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G M Gilad

Publications and source records attributed to G M Gilad.

88 records · Page 5Linked to original sources
PubMed1980

Failure to detect collateral sprouting of mesolimbic dopaminergic neurons during early postnatal development.

Using biochemical parameters the present study sought to assess the normal developmental pattern of the dopaminergic innervation of the olfactory tubercle (OT) and how it is affected by olfactory bulbectomy. In rats, the adult pattern of cellular organization is achieved in the OT gradually over the first 7 days after birth. On the other hand, tyrosine hydroxylase (TH) and [3H]dopamine ([3H]DA) uptake, while present at low levels, start to increase rapidly only after the first 7 days reaching adult levels by 40 and 20 days after birth, respectively. TH in dopamine (DA) cell bodies of A10 was already high, 40% of adult value, at birth, reached 150% by day 14 and decreased back to adult values by day 21 after birth. In 10-day-old rats, bulbectomy resulted, 30 days later, in an increase to 123% of control in TH activity and 137% in [3H]DA uptake within the OT. Comparable changes were found following bulbectomy in adults. However, bulbectomy in 1-day-old rats did not produce any significant changes 40 days later. The findings suggest that during postnatal growth TH activity is increased in DA cell bodies, preceding the changes in DA terminals of the OT, resembling the changes occurring during collateral sprouting in adults. In addition, changes indicative of collateral sprouting do not occur in response to deafferentation of the OT in 1-day-olds but do in 10-day-olds or older animals, a phenomenon probably related to a critical development period of the OT.

Aging↗
PubMed1979

Collateral sprouting in central mesolimbic dopamine neurons: biochemical and immunocytochemical evidence of changes in the activity and distrubution of tyrosine hydroxylase in terminal fields and in cell bodies of A10 neurons.

The olfactory tubercle of adult rats was examined for the development of collateral sprouts from intrinsic dopaminergic axons following unilateral olfactory bulbectomy. In the ipsilateral tubercle tyrosine hydroxylase (TH) activity began to increase by 10-14 days following the lesion, gradually reaching a maximum of 125% of control (P less than 0.005) by 21 days where it remained permanently elevated. The rise of TH activity in the tubercle reflected changes of the dopaminergic innervation, since dopamine-beta-hydroxylase (DBH) activity was unchanged, and lesions of the dorsal noradrenergic bundle reduced DBH but not TH activity in the tubercle. By immunocytochemical staining the elevation of TH reflected an increased number and altered distribution of TH-containing processes within the olfactory tubercle. By 30 days the uptake of [3H]dopamine into synaptosomes of the olfactory tubercle was also increased to 140% of control (P less than 0.05). In the dopaminergic cell bodies of the ipsilateral A10 group (which innervate the tubercle) TH activity was transiently elevated to 121% (P less than 0.05) by 4 days, returning to control levels by 10 days. Histologically no change in activity was detected. The results indicate that mesolimbic dopaminergic neurons of A10 which innervate the olfactory tubercle will sprout in response to removal of a major non-dopaminergic input, that the new innervation is sustained, and that during collateral sprouting there is a transient elevation of TH activity in the uninjured cell bodies which precedes the period of axonal growth. The activity in the uninjured cell bodies which precedes the period of axonal growth. The findings suggest that (a) the increase of TH activity in the A10 cell bodies during collateral sprouting may be a reflection of an increase in the amount of enzyme protein required for transport into the enlarging terminal fields, (b) that as in development sprouts are in place before they reach biochemical maturity, (c) the biochemical mechanisms underlying collateral sprouting of uninjured neurons are not necessarily the same as those associated with regenerative sprouting in response to axonal injury, and (d) the development and the acquisition of biochemical maturation of collateral sprouts in the CNS involves complex two-way signaling between terminal field and cell bodies. The development of collateral sprouts of dopaminergic neurons may be the cellular substrate of the development of behavioral hyperactivity and aggression produced by bilateral olfactory bulbectomy in rat.

Animals↗
PubMedDate not supplied

Polyamines in rat brain extracellular space after ischemia.

This article reports measurements of extracellular polyamines in rat brain. Microdialysis probes were implanted in the striatum and microperfusion samples were collected before, during, and after transient (20 min) global ischemia. Polyamine levels in microperfusates were measured by reverse-phase high-performance liquid chromatography after precolumn derivatization. No significant changes in extracellular polyamines were detected for up to 3 h following ischemia. We conclude that extracellular levels of polyamines (1) are comparable to the low levels in other extracellular compartments, and (2) do not change during the initial period of reperfusion, the period most critical for neuron survival after ischemia.

Animals↗
PubMedDate not supplied

Accumulation of exogenous polyamines in gerbil brain after ischemia.

Regionally selective delayed neuronal degeneration is a characteristic sequel of cerebral ischemia. Recent evidence indicates that changes in brain polyamine metabolism may be critical for nerve cell survival after ischemia. Within hours after ischemia, intracellular putrescine levels are greatly increased and remain elevated for days, whereas only minor changes are noted in the levels of the polyamines spermine and spermidine. In contrast, the extracellular levels of all polyamines are low after ischemia. Injections of polyamines following ischemia, however, can protect neurons in the gerbil brain from delayed cell death, with spermine being the most potent of the polyamines. In the present study, therefore, we sought to determine if increased polyamine uptake occurs in the brain after ischemia. In the hippocampal slice preparation, temperature-dependent uptake was unique for spermine, but not for spermidine or putrescine. Uptake of [14C]spermine was transiently increased after ischemia, peaking at 150% of control by 12-13 h and subsiding by 24 h. Intravenous injections of [3H]spermidine resulted in a postischemic accumulation of this polyamine throughout the forebrain parenchyma. We conclude that: 1. Active cellular uptake of spermine is transiently increased early after ischemia; 2. A nonspecific accumulation of exogenous polyamines occurs early after ischemia probably owing to a compromised blood-brain barrier, and 3. The findings indicate that exogenous polyamines can exert their effect directly in the brain after ischemia.

Animals↗
PubMedDate not supplied

Selective influence of rat genotype on age-related regional changes in forebrain muscarinic binding.

Muscarinic binding was analyzed in the hippocampus and frontal cerebral cortex of 3 (young) and 24-month-old (aged) inbred Wistar-Kyoto (WKY), Brown-Norway (BN) and Lewis rats, by the specific binding of the antagonist quinuclidinylbenzilate (QNB). While no age-related changes were detected in the hippocampus of all strains, complex changes were found in the cortex. Maximal binding capacity (Bmax) of [3H]QNB was decreased in the cortex of aged WKY rats, remained unchanged in the BN strain and was elevated in Lewis rats. We conclude that regional differences exist in age-related changes in forebrain muscarinic binding which are probably due to differences in the types and connections of cholinoceptive neurons in these regions. The results suggest that it is the rate of these changes which is affected by the rat genotype.

Aging↗
PubMedDate not supplied

Age-related reduction in pituitary corticotropin-releasing hormone receptors in two rat strains.

Open field behavior and age-related changes in anterior pituitary corticotropin-releasing hormone (CRH) receptors, as well as plasma ACTH levels, were measured in two inbred rat strains. The strains utilized were Wistar Kyoto (WKY) and Brown-Norway (BN), the former characterized by shorter life-span and hyper-reactivity to stressors as compared to the latter. Behaviorally, WKY rats showed hyper-responsivity to a novel environment as indicated by their delay in entering the open field, increased grooming, reduced rearing, and reduced locomotion. These strain-dependent behavioral differences were not affected by aging. The binding capacity of CRH receptors was similar in both strains and Bmax values were decreased (25-27%) with aging, with no changes in Kd values. In contrast, plasma ACTH levels were 67% higher in WKY than in BN rats but did not change with aging. Thus, despite pituitary CRH receptor down regulation, plasma ACTH levels following decapitation were sustained during aging. This suggests the presence of some compensatory factors in the hypothalamic-pituitary axis regulation which sustain ACTH response during aging. Furthermore, the findings indicate that higher plasma ACTH levels and hyper-reactivity to a novel environment are inversely correlated with longevity in the rat.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

Developmental regulation of the brain polyamine-stress-response.

A transient increase in brain polyamine metabolism, termed the polyamine-stress-response is a common response to stressful stimuli. Previous studies have implicated an over-reactive polyamine response as a component of the maladaptive brain response to stressful events, and as a novel molecular mechanism involved in the pathophysiology of affective disorders. Ample evidence indicates that stressful experiences during early life can alter normal developmental processes and may result in pathophysiological and behavioral changes in the adult. Additionally, an important characteristic of affective disorders is their age dependency, a phenomenon that may be correlated with a maladaptive regulation of the hypothalamic-pituitary-adrenocortical (HPA) neuroendocrine system. In the present study we measured the activities of the enzymes ornithine decarboxylase and S-adenosylmethionine decarboxylase as markers of polyamine synthesis and found that unlike adults, immature rats do not show the characteristic brain polyamine-stress-response. Instead of the characteristic increase observed in adults, ornithine decarboxylase activity in immature animals was reduced or remained unchanged (for up to 16 days of age) after a dexamethasone injection or restraint stress application. The ontogenesis of this ornithine decarboxylase response was brain region-specific, indicating its dependence on the stage of neuronal maturation. Animals treated with dexamethasone at 7 days of age, showed increased behavioral reactivity in the open-field test as adults and an attenuated increase in ornithine decarboxylase activity after a re-challenge with dexamethasone at age 60 days. The results indicate that: (1) the brain polyamine-stress-response is developmentally regulated and its ontogenesis is brain region-specific, indicating dependence on the stage of neuronal maturation; (2) the switch to a mature polyamine-stress-response pattern coincides with the cessation of the stress hyporesponsive period in the HPA system: (3) activation of the polyamine-stress-response, as in the mature brain, appears to be a constructive reaction, while its down-regulation, as in the developing brain, may be implicated in neuronal cell death; (4) an attenuated dexamethasone-induced increase in ornithine decarboxylase activity implicates an altered polyamine-stress-response in the maladaptive response of the brain to stressful events.

Adenosylmethionine Decarboxylase↗