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PubMed2005

Constitutive Dyrk1A is abnormally expressed in Alzheimer disease, Down syndrome, Pick disease, and related transgenic models.

DYRK1A, dual-specificity tyrosine-regulated kinase 1A, maps to human chromosome 21 within the Down syndrome (DS) critical region. Dyrk1 phosphorylates the human microtubule-associated protein tau at Thr212 in vitro, a residue that is phosphorylated in fetal tau and hyper-phosphorylated in Alzheimer disease (AD) and tauopathies, including Pick disease (PiD). Furthermore, phosphorylation of Thr212 primes tau for phosphorylation by glycogen synthase kinase 3 (GSK-3). The present study examines Dyrk1A in the cerebral cortex of sporadic AD, adult DS with associated AD, and PiD. Increased Dyrk1A immunoreactivity has been found in the cytoplasm and nuclei of scattered neurons of the neocortex, entorhinal cortex, and hippocampus in AD, DS, and PiD. Dyrk1A is found in sarkosyl-insoluble fractions which are enriched in phosphorylated tau in AD brains, thus suggesting a possible association of Dyrk1A with neurofibrillary tangle pathology. Yet, no clear relationship has been observed between tau phosphorylation at Thr212, and GSK-3 and Dyrk1A expression in diseased brains. Transgenic mice bearing a triple tau mutation (G272V, P301L, and R406W) and expressing hyper-phosphoyrylated tau in neurons of the entorhinal cortex, hippocampus, and cerebral neocortex show increased expression of Dyrk1A in individual neurons in the same regions. However, transgenic mice over-expressing Dyrk1A do not show increased phosphorylation of tau at Thr212, thus suggesting that Dyrk1A over-expression does not trigger per se hyper-phosphorylation of tau at Thr212 in vivo. The present observations indicate modifications in the expression of constitutive Dyrk1A in the cytoplasm and nuclei of neurons in various neurodegenerative diseases associated with tau phosphorylation.

Adult↗
PubMed1999

Direct demonstration of persistent Na+ channel activity in dendritic processes of mammalian cortical neurones.

1. Single Na+ channel activity was recorded in patch-clamp, cell-attached experiments performed on dendritic processes of acutely isolated principal neurones from rat entorhinal-cortex layer II. The distances of the recording sites from the soma ranged from approximately 20 to approximately 100 microm. 2. Step depolarisations from holding potentials of -120 to -100 mV to test potentials of -60 to +10 mV elicited Na+ channel openings in all of the recorded patches (n = 16). 3. In 10 patches, besides transient Na+ channel openings clustered within the first few milliseconds of the depolarising pulses, prolonged and/or late Na+ channel openings were also regularly observed. This 'persistent' Na+ channel activity produced net inward, persistent currents in ensemble-average traces, and remained stable over the entire duration of the experiments ( approximately 9 to 30 min). 4. Two of these patches contained < or = 3 channels. In these cases, persistent Na+ channel openings could be attributed to the activity of one single channel. 5. The voltage dependence of persistent-current amplitude in ensemble-average traces closely resembled that of whole-cell, persistent Na+ current expressed by the same neurones, and displayed the same characteristic low threshold of activation. 6. Dendritic, persistent Na+ channel openings had relatively high single-channel conductance ( approximately 20 pS), similar to what is observed for somatic, persistent Na+ channels. 7. We conclude that a stable, persistent Na+ channel activity is expressed by proximal dendrites of entorhinal-cortex layer II principal neurones, and can contribute a significant low-threshold, persistent Na+ current to the dendritic processing of excitatory synaptic inputs.

Algorithms↗
PubMed2004

Repair of the entorhino-hippocampal projection in vitro.

The repair of axonal projections and the reconstruction of neuronal circuits after CNS lesions or during neurodegenerative disease are major challenges in restorative neuroscience. We have explored the potential of transplanted immature neurons to repair a specific axonal projection in an entorhino-hippocampal slice culture model system. When slices of immature entorhinal cortex (EC) from tau-GFP transgenic mice were cultured next to slices from postnatal hippocampus, an axonal projection from the E18 embryonic entorhinal cortex to the dentate gyrus of the postnatal hippocampus developed, which was similar to that observed in control cultures. Even more immature neuronal precursors in slices from E15 developing cerebral cortex differentiated and established an axonal projection to the hippocampal slice. This projection terminated specifically in the outer molecular layer of the dentate gyrus, the normal target area of the entorhino-hippocampal projection. When embryonic tissue from the presumptive brainstem area was used, there was still a subpopulation of fibers with a specific termination in the outer molecular layer, but few specific fibers were found in cocultures with embryonic midbrain. Our results show that very immature cortical neurons are potentially able to form an entorhino-hippocampal projection that terminates in a correct lamina-specific fashion in the dentate gyrus. These findings support the idea that immature neuronal precursor cells could be used for the reconstruction of specific neuronal circuits.

Animals↗
PubMed1997

Lateral entorhinal, perirhinal, and amygdala-entorhinal transition projections to hippocampal CA1 and dentate gyrus in the rat: a current source density study.

In urethane-anesthetized rats, cortical regions which provide distal dendritic excitation of the dentate gyrus and CA1 of the dorsal hippocampus were studied using current source density analysis. Electrical stimulation of the lateral perforant path (LPP) in the lateral angular bundle, lateral entorhinal cortex (LEC), and amygdala-entorhinal transition (TR) resulted in a current sink in the outer molecular layer of the dentate gyrus accompanied by proximal sources; this sink-source pattern is distinctly different from the source-sink-source pattern evoked by medial perforant path stimulation. The progressive decrease of the sink latency following stimulation of the TR, LEC, and LPP (11.6, 7.8, and 3.6 ms, respectively, at the dorsal blade of the dentate gyrus) suggests a possible sequence of orthodromic activation of these structures. Stimulation of the LEC or TR (collectively termed cortical stimulation) differed from LPP (fiber) stimulation. A low threshold and small chronaxie were characteristic of fiber rather than cortical stimulation. In addition, cortical stimulation, possibly through excitation of intracortical circuits, evoked larger paired-pulse facilitation of the excitatory postsynaptic currents in dentate gyrus and more symmetric excitation of the dorsal and ventral blades of the dentate gyrus as compared to fiber stimulation. Stimulation of the perirhinal cortex (PRh) evoked a short-latency sink in the outer molecular layer of the dentate gyrus with no paired-pulse facilitation, similar to fiber stimulation. A distal dendritic CA1 sink was observed after LPP but not after PRh stimulation. An ibotenic acid injection that lesioned almost all the cells in the perirhinal cortex confirmed the hypothesis that PRh stimulation activated fibers of passage, perhaps in the rostral ventrolateral angular bundle. We conclude that the PRh does not provide a significant excitatory input to the DG or CA1. We have found distinct dendritic excitation of the dentate gyrus by the lateral versus medial perforant paths, and by fiber (LPP and MPP) versus cortical (LEC and TR) stimulation. We also emphasize that processing in the entorhinal cortex is important in the temporal shaping of the signals afferent to the hippocampus.

Amygdala↗
PubMed1991

Beta-adrenergic receptor distribution in human and rat hippocampal formation: marked species differences.

The topography of beta-adrenergic receptors in the rat and human hippocampal formation was assessed by in vitro binding of 125I-pindolol to tissue sections. Marked differences were found in the distribution of beta-adrenergic receptors and in the relative amounts of beta 1 and beta 2 receptor subtypes in the two species. In the human, the highest receptor densities were present in the pyramidal cell layer and in the stratum lacunosum-moleculare. In the rat hippocampus, those regions contained the lowest densities of 125I-pindolol binding sites. The highest densities of beta-adrenergic receptors in the rat hippocampal formation were found in the ventral subiculum and in the entorhinal cortex. In contrast, in the human hippocampus, the subiculum and entorhinal cortex contained relatively low densities of the receptors. Competition studies with beta 1- and beta 2-selective antagonists revealed that beta 2-adrenergic receptors predominate in the human hippocampus and beta 1-adrenergic receptors predominate in the rat hippocampus. The marked species differences observed suggest that the pharmacological responsivity of the hippocampus to adrenergic agents and the role of noradrenaline in regulation of hippocampal function could be very different in rats compared to humans.

Animals↗
PubMed2006

Neural circuits mediating latent learning and conditioning for salt in the rat.

Male Long-Evans rats alternately drank a salt solution in one distinctive compartment of a conditioned cue preference (CCP) apparatus and water in a different compartment over 8 days (training trials) and were then given a choice between the two compartments with no solutions present (test trial). Rats that were water deprived during training, then salt+water deprived during testing, spent more time in their salt-paired compartments, a salt latent cue preference (LCP). Rats that were water-only deprived during training and testing spent more time in their water-paired compartments, a water CCP. Rats that were salt+water deprived during both training and testing spent more time in their salt-paired compartments, a salt CCP. Bilateral, pre-training lesions of the lateral amygdala impaired the water and salt CCPs but not the salt LCP, reflecting the role of the amygdala in Pavlovian conditioning. Lesions of the dorsal or ventral hippocampus impaired the salt LCP and the water and salt CCPs, possibly reflecting the role of the hippocampus in contextual learning. Lesions of the fimbria-fornix impaired the water and salt CCPs but not the salt LCP, while lesions of the entorhinal cortex impaired the salt LCP but not the CCPs. This suggests that the LCP depends on a circuit that includes dorsal and ventral hippocampus and entorhinal cortex, a major conduit of sensory information from the cortex. In contrast, the CCPs depend on the amygdala and a circuit that includes the hippocampus and fimbria-fornix, possibly as a conduit of motivational information from subcortical structures.

Amygdala↗
PubMed1996

Cholinergic innervation of the primate hippocampal formation: II. Effects of fimbria/fornix transection.

The distribution of choline acetyltransferase (ChAT)-immunoreactive and acetylcholinesterase (AChE)-positive fibers and terminals was analyzed in the hippocampal formation of macaque monkeys subjected to transection of the fimbria/fornix. Cases with either unilateral or bilateral transections were prepared, with post transection survival times ranging from 2 weeks to 1.5 years. The fimbria/fornix transection resulted in a dramatic decrease in the number of cholinergic fibers in most regions of the hippocampal formation. Some hippocampal regions, however, showed relatively greater sparing of ChAT- or AChE-positive fibers. In practically all regions of the hippocampal formation, residual AChE-positive fibers were more abundant than ChAT-immunoreactive fibers. In animals with unilateral lesions, the distribution patterns and density of AChE and ChAT staining on the side contralateral to the lesion were generally similar to those of sections from unlesioned control brains. The largest decreases in the densities of positive fibers were observed in the dentate gyrus, CA3 and CA2 fields of the hippocampus, subiculum, parasubiculum, and medial and caudal parts of the entorhinal cortex. Fibers were relatively better preserved in the rostral or uncal portion of the hippocampus and dentate gyrus and in the rostral portion of the entorhinal cortex. The presubiculum demonstrated remarkable sparing that contrasted with the almost complete loss of fibers in the parasubiculum. Interestingly, animals killed approximately 1.5 years after the fornix transection showed essentially the same pattern of fiber loss as the cases with shorter survival periods. This indicates that the residual ChAT-immunoreactive fibers, many of which reach the hippocampal formation through a ventral cholinergic pathway, are not capable of reinnervating the denervated portions of the hippocampal formation. This appears to distinguish the monkey from the rat, for which substantial sprouting and reinnervation of cholinergic fibers have been reported after similar lesions.

Acetylcholinesterase↗
PubMed1999

Level of sustained entorhinal activity at study correlates with subsequent cued-recall performance: a functional magnetic resonance imaging study with high acquisition rate.

Functional magnetic resonance imaging (fMRI) with high acquisition rate was performed during the intentional memorizing of words to specify which medial temporal lobe structure is important in determining what words are subsequently remembered in a cued-recall test and to characterize the time course of activation in that structure. Functional images of six healthy young subjects were analyzed by two subject- and voxel-wise statistics: First, to identify brain areas transiently engaged in encoding of words, brain activity during memorizing visually presented words and watching a fixation cross was compared by a Kolmogorov-Smirnov statistic (KS-test). Second, to identify brain areas whose activity correlates with memory encoding success, a Kendall's correlation was calculated between signal intensity at study and performance in a subsequent cued-recall test. Averaged signal intensities were plotted as a function of time to depict the time course of brain activity detected by both statistical tests. The level of slowly modulated, sustained activity in Brodmann area 28 (entorhinal cortex) did not respond transiently as study words appeared, but did correlate positively with subsequent test performance. More left than right activity in Brodmann area 45 (dorso-lateral prefrontal cortex) and bilateral activity in Brodmann area 44 (premotor cortex) exhibited transient hemodynamic responses that did not show any relation to subsequent memory performance. Thus, the study identified a novel pattern of slowly modulated brain activity in human entorhinal cortex that may represent a declarative memory encoding state whose level predicts whether experiences will be remembered or forgotten.

Adult↗
PubMed2005

Physiological changes in chronic epileptic rats are prominent in superficial layers of the medial entorhinal area.

PURPOSE: We investigated whether the functional network properties of the medial entorhinal area (MEA) of the entorhinal cortex were altered in a rat model of chronic epilepsy that is characterized by extensive cell loss in MEA layer III. METHODS: Responses were evoked in the entorhinal cortex by electrical stimulation of the subiculum in anesthetized chronic epileptic rats, 2-4 months after status epilepticus, induced by systemic kainate (KA) injections. Laminar field potentials were measured using a 16-channel silicon probe that covered all six layers of the MEA; an estimate of the local transmembrane currents was made using current source density analysis. RESULTS: Double-pulse stimulation of the subiculum evoked responses in deep and superficial layers of the MEA in control and KA rats. A current sink in layer I and at the border of layer I and II that was induced by antidromic activation of MEA-II, was much more prominent in KA rats with extensive neuronal loss in MEA-III than in control rats or KA rats with minor MEA-III loss. Furthermore, KA rats that displayed MEA-III loss presented a series of oscillations induced by subicular stimulation in the beta/gamma-frequency range (20-100 Hz), which were confined to superficial layers of MEA. These oscillations were never observed in control rats or KA rats with minor MEA-III loss. CONCLUSIONS: These results indicate that the observed alterations in the superficial MEA responses to subiculum stimulation and the occurrence of beta/gamma-oscillations are related phenomena, which are a consequence of altered and impaired inhibition within these MEA layers in chronic epileptic rats.

Animals↗
PubMed2001

Selective cytotoxic lesions of the retrohippocampal region produce a mild deficit in social recognition memory.

Although a number of studies have implicated the hippocampal formation in social recognition memory in the rat, a recent study in this laboratory has demonstrated that selective cytotoxic lesions, confined to the hippocampus proper (encompassing the four CA subfields and the dentate gyrus), are without effect on this behaviour. This finding suggests that the hippocampus proper does not subserve social recognition memory in the rat, but does not preclude the possibility that other areas of the hippocampal formation, such as the entorhinal cortex or subiculum, could support this form of learning. The present study addressed this issue by examining the effects of selective cytotoxic retrohippocampal (RHR) lesions (including both the entorhinal cortex and subiculum) on social recognition memory in the rat. RHR lesions produced a mild social recognition memory impairment, although lesioned animals still displayed a reduction in investigation time between the first and second exposure to the juvenile. This result is consistent with other studies which have implicated the retrohippocampal or parahippocampal area in olfactory recognition memory processes. It also suggests, however, that other areas, out with the retrohippocampal region, are also likely to play an important role in social recognition memory.

Age Factors↗
PubMed2003

Parallel compensatory and pathological events associated with tau pathology in middle aged individuals with Down syndrome.

Aged individuals with Down syndrome (DS) develop senile plaques and neurofibrillary tangles consistent with Alzheimer disease (AD). Prior to or in parallel with AD pathology, compensatory growth responses may occur. Immunohistochemistry and confocal microscopy studies in the hippocampus from 15 individuals ranging in age from 5 months to 67 years compared markers of normal and abnormal tau accumulation (phosphorylated tau [AT8, MC-1], tau-1, N-terminal tau) with the extent and location of neuronal growth marker immunoreactivity (BDNF, GAP-43, MAP-2). In middle age (30-40 years), prior to entorhinal neuron loss, the earliest tau accumulation occurred in the outer molecular layer (OML), which was consistent with both pathological and compensatory fetal tau expression. These events were followed at a later age, associated with entorhinal neuron loss, by an increase in GAP-43. Hilar neurons exhibiting a sprouting morphology were also noted. Age-dependent observations in the DS brain in the current study parallel hippocampal compensatory responses described in entorhinal cortex lesion studies in rodents. Thus, compensatory growth responses may occur in DS prior to extensive AD pathology and may be one mechanism underlying observations in PET studies of hypermetabolism in the entorhinal cortex of individuals with DS.

Adolescent↗
PubMed1987

The afferent input to the magnocellular division of the mediodorsal thalamic nucleus in the monkey, Macaca fascicularis.

The origin and termination of fibers to the mediodorsal thalamic nucleus, especially those to the medial, magnocellular part of the nucleus (MDm), have been studied using anterograde and retrograde axonal tracing methods, as well as electrophysiological recording. The results indicate that in addition to its well-known connections to and from the prefrontal cortex, MDm receives fibers from many parts of the basal forebrain, including the ventral pallidum and other parts of the substantia innominata, the amygdaloid complex, the primary olfactory cortex, entorhinal and perirhinal cortex, and the cortex at the pole of the temporal lobe. Lighter projections arise in the subiculum, the ventral insula, and the superior and inferior temporal gyri. The cells that project to MDm tend to be large, polymorphic neurons. Throughout most of the basal forebrain they are diffusely distributed through several nuclei or cortical layers, without obvious relation to nuclear or laminar boundaries. The major exception to this is in the ventral pallidum, where there is a dense concentration of cells that project to MDm. The lateral part of the mediodorsal nucleus (MDl) receives few if any fibers from the basal forebrain and temporal lobe, but is innervated by several brainstem structures, especially the superior colliculus, the substantia nigra, the medial vestibular nucleus, and the midbrain tegmental fields. In MDm, the fibers are distributed in irregular patches. Three-dimensional analysis indicates that these patches are often clustered into separate bands or columns at different anteroposterior levels. In addition, the strongest projections from the three major regions that innervate MDm are organized in a complex three-dimensional pattern. First, the fibers from the amygdaloid nuclei terminate most heavily (but not exclusively) in the rostral third of MDm. The parvicellular accessory basal amygdaloid nucleus and the amygdalohippocampal area project principally to the dorsal part of the nucleus. The parvicellular basal nucleus and the periamygdaloid cortex project to the ventromedial quadrant of MDm; and the magnocellular basal nucleus, the magnocellular accessory basal nucleus, and the lateral nucleus all project to the ventrolateral quadrant. Second, the substantia innominata projects preferentially to the caudal part of MDm. The medial part of the substantia innominata, especially the ventral pallidum, innervates the dorsomedial quadrant, while more caudal and lateral areas of this region project ventrolaterally. Third, the projections arising from the entorhinal and other temporal cortical areas terminate primarily in the mid-rostrocaudal level of MDm.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗
PubMed2000

Cortico-hippocampal communication by way of parallel parahippocampal-subicular pathways.

The hippocampal memory system, consisting of the hippocampal formation and the adjacent parahippocampal region, is known to play an important role in learning and memory processes. In recent years, evidence from a variety of experimental approaches indicates that each of the constituting fields of the hippocampal memory system may serve functionally different, yet complementary roles. Understanding the anatomical organization of cortico-parahippocampal-hippocampal connectivity may lead to a further understanding of these potential functional differences. In the present paper we present the two main conclusions of experiments in which we studied the anatomical organization of the hippocampal memory system of the rat in detail, with a focus on the pivotal position of the entorhinal cortex. We first conclude that the simple traditional view of the entorhinal cortex as simply the input and output structure of the hippocampal formation needs to be modified. Second, our data indicate the existence of two parallel pathways through the hippocampal memory system, arising from the perirhinal and postrhinal cortex. These two parallel pathways may be involved in separately processing functionally different types of sensory information. This second proposition will be subsequently evaluated on the basis of series of electrophysiological studies we carried out in rats and some preliminary functional brain imaging studies in humans.

Animals↗
PubMed1989

Neurochemical characteristics of aluminum-induced neurofibrillary degeneration in rabbits.

Aluminum-induced neurofibrillary degeneration in rabbits is known to affect particular populations of neurons. The neurotransmitter alterations which accompany aluminum neurofibrillary degeneration were examined in order to assess how closely they mimic those of Alzheimer's disease. There was a significant reduction in choline acetyltransferase activity in entorhinal cortex and hippocampus as well as significant reductions in cortical concentrations of serotonin and norepinephrine in the aluminum-treated rabbits. Significant reductions in glutamate, aspartate and taurine were found in frontoparietal and posterior parietal cortex. Concentrations of GABA were unchanged in cerebral cortex. Both substance P and cholecystokinin immunoreactivity were significantly reduced in entorhinal cortex but there were no significant changes in somatostatin, neuropeptide Y and vasoactive intestinal polypeptide. The five neuropeptides were unaffected in striatum, thalamus, cerebellum and brainstem. Neurochemical changes were found in the regions with the most neurofibrillary degeneration while regions with little or no neurofibrillary degeneration were unaffected. The reductions in choline acetyltransferase activity, serotinin and noradrenaline suggest that some neuronal populations preferentially affected in Alzheimer's disease are also affected by aluminum-induced neurofibrillary degeneration; however, the cortical somatostatin deficit which is a feature of Alzheimer's disease is not replicated in the aluminum model.

Aluminum↗
PubMed1998

Mesial temporal lobe measurements on magnetic resonance imaging scans.

Changes in the mesial temporal lobe, particularly in the hippocampus, amygdala, and entorhinal cortex, are reported to occur in several neuropsychiatric conditions. Neuroimaging provides a non-invasive means of studying these changes. We present a method for reliably measuring the hippocampus, amygdala, and entorhinal cortex on MRI. The advantages of our method include high reliability, the use of orthogonal views in delineating boundaries and circumscription of measurement such that no tissue of any one anatomic structure is included in the measurement of another structure.

Amygdala↗
PubMed1990

Systemic injection of kainic acid: gliosis in olfactory and limbic brain regions quantified with [3H]PK 11195 binding autoradiography.

Neurodegenerative diseases may result from excessive stimulation of excitatory amino acid receptors by endogenous ligands. Because neuronal degeneration is associated with glial proliferation and hypertrophy, the degenerative changes throughout rat brain following the systemic administration of kainic acid (12 mg/kg) were mapped with quantitative autoradiography of [3H]PK 11195. This radioligand binds to a mitochondrial benzodiazepine binding site (MBBS) on microglia and astrocytes. Analysis of eight horizontal and four coronal brain levels revealed up to 16-fold increases in [3H]PK 11195 binding from 1 to 5 weeks but not 1 day after kainate injection. Increases in [3H]PK 11195 binding were predominantly in ventral limbic brain regions and olfactory projections to neocortical areas, with the olfactory cortex greater than subiculum/CA1 greater than anterior olfactory nucleus, medial thalamic nucleus, and piriform cortex greater than cingulate cortex and rostral hippocampus greater than dentate gyrus, septum, and amygdala greater than entorhinal cortex and temporal cortex. Little or no enhancement of [3H]PK 11195 binding was observed in numerous regions including the caudate-putamen, substantia nigra, nucleus accumbens, olfactory tubercle, cerebellum, thalamic nuclei, choroid plexus, medulla, parietal or occipital cortex, or pons. A 2-fold greater extent of neurodegeneration was obtained in ventral portions of the olfactory bulb, entorhinal cortex, temporal cortex, and dentate gyrus compared with the dorsal portions of these structures. The pattern of increase in [3H]PK 11195 binding closely matched the patterns of neuronal degeneration reported following parenteral kainate injection. These findings strengthen the notion that quantitative autoradiography of [3H]PK 11195 is a valuable tool to quantify the extent of neuronal degeneration. Furthermore, the quantitative changes in [3H]PK 11195 binding in different limbic structures parallel their relative variation in neuropathology observed in Alzheimer's disease but not Huntington's chorea. These findings are in agreement with the idea that excessive stimulation of excitatory amino receptors may contribute to the etiology of Alzheimer's disease.

Animals↗
PubMed2003

Neuron-specific age-related decreases in dopamine receptor subtype mRNAs.

Age-related decline in dopamine receptor levels has been observed in regional studies of animal and human brains; however, identifying specific cellular substrates and/or alterations in distinct neuronal populations remains elusive. To evaluate whether age-related decreases in dopamine receptor subtypes are associated with specific cell populations in the hippocampus and entorhinal cortex, antisense RNA amplification was combined with cDNA array analysis to examine effects of aging on D1-D5 dopamine receptor mRNA expression levels in hippocampal CA1 pyramidal neurons and entorhinal cortex layer II stellate cells from post-mortem human brains (19-92 years). In CA1 pyramidal neurons, significant age-related decline was observed for dopamine receptor mRNAs (D1-D4, P < 0.001; D5, P < 0.05) but not for the cytoskeletal elements beta-actin, three-repeat (3R) tau, and four-repeat (4R) tau. In contrast, no significant changes were observed in stellate cells across the same cohort. Thus, senescence may be a factor responsible for cell-specific decrements in dopamine receptor gene expression in one population of neurons within a circuit that is critical for learning and memory. Furthermore, these results support the hypothesis that alterations in dopaminergic function may also be related to behavioral abnormalities, such as psychosis, that occur with aging.

Adult↗
PubMed1994

The differentiation of depression from dementia by temporal lobe magnetic resonance imaging.

Temporal lobe Magnetic Resonance Imaging (MRI) was performed in 43 patients with NINCDS/ADRDA Alzheimer's disease (AD) (33 probable, 7 possible, 3 definite) and 32 subjects with DSM-III-R Major Depression (DEP) matched for age, sex and level of education. Hippocampus (anterior and posterior, right and left), amygdala, entorhinal cortex, parahippocampal gyrus and cerebral cortex were rated for atrophy on a 4-point scale. Good discrimination between groups could be achieved using a cut-off of 2 or more on anterior hippocampal atrophy rating (sensitivity 93%; specificity 84%; 89% cases correctly grouped overall). Even among a subgroup of 9 mild AD subjects and 10 cognitively impaired DEP subjects (matched on mini-mental state score), the same cut-off correctly grouped 84% (16/19) cases. Hippocampal atrophy increased with age in both AD and DEP subjects leading to a reduction in specificity (but not sensitivity) for those aged over 75. Within the AD group a significant correlation was observed between length of history and atrophy of the entorhinal cortex (r = 0.39, P = 0.009). We conclude that temporal lobe atrophy on MRI can provide good discrimination between AD and DEP subjects, including those DEP patients with cognitive impairment apparent on screening tests of cognitive function.

Aged↗