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B J Hoffer

Publications and source records attributed to B J Hoffer.

At least 37 records · Page 2Linked to original sources
PubMed2000

Vitamin D(3) attenuates cortical infarction induced by middle cerebral arterial ligation in rats.

We have previously reported that intracerebral administration of glial cell line derived neurotrophic factor (GDNF) reduces the extent of middle cerebral arterial (MCA) ligation-induced cortical infarction in rats. Recent studies have shown that application of 1, 25 dihydroxyvitamin D(3) (D3) enhances GDNF mRNA expression in vitro. The purpose of the present study was to investigate if administration of D3 in vivo will protect against ischemic brain injury. Adult male Sprague-Dawley rats were injected daily with D3 or with saline for four or eight days. Animals received a 90-min right MCA ligation on the 4(th) or 8(th) day after anesthesia with chloral hydrate. Animals were sacrificed for tri-phenyl-tetrazolium chloride (TTC) staining 24 h after the onset of reperfusion. A subset of animals receiving eight days of D3 or saline treatment were used for blood gas and cerebral GDNF protein level analysis. We found that pretreatment with D3 for four days did not attenuate the ischemic injury. However, animals receiving eight days of D3 injections showed a significant reduction in the amount of infarction in the cortex. Eight day D3 treatment did not alter blood gases or blood pressure; however, it did increase calcium levels. Pretreatment with D3 significantly increased GDNF levels in the cortex. In conclusion, our data indicate that D3 reduces ischemia-induced brain damage and supports the hypothesis that this effect may be through the up-regulation of GDNF mechanisms in cortex.

Animals↗
PubMed2000

Hyperbaric oxygen therapy for treatment of postischemic stroke in adult rats.

The efficacy of hyperbaric oxygen (HBO) therapy for treatment of stroke remains to be validated in the laboratory. We report here that adult rats subjected to occlusion of the middle cerebral artery and subsequently exposed to HBO (3 atm, 2 x 90 min at a 24-h intervals; animals terminated shortly after the second treatment) or hyperbaric pressure (HBP; 3 atm, 2 x 90 min at a 24-h interval; animals terminated shortly after the second treatment) immediately after the ischemia or after a 60-min delay generally displayed recovery from motor deficits at 2.5 and 24 h of reperfusion, as well as a reduction in cerebral infarction at 24 h of reperfusion compared to ischemic animals subjected to normal atmospheric pressure. While both HBO and HBP treatments promoted beneficial effects, HBO produced more consistent protection than HBP. Treatment with HBO immediately or 60 min after reperfusion equally produced significant attenuations of cerebral infarction and motor deficits. In contrast, protective effects of HBP treatment against ischemia were noted only when administered immediately after ischemia, which resulted in a significantly reduced infarction volume, but only produced a trend toward decreased behavioral deficits. The present results demonstrate that HBO and, to some extent, HBP reduced ischemic brain damage and behavioral dysfunctions.

Age Factors↗
PubMed2000

Glial cell line-derived neurotrophic factor receptor alpha1 availability regulates glial cell line-derived neurotrophic factor signaling: evidence from mice carrying one or two mutated alleles.

Glial cell line-derived neurotrophic factor receptor alpha1 (GFRalpha1, also known as GDNFR-alpha) is a glycolipid-anchored membrane protein of the GFRalpha family, which binds glial cell line-derived neurotrophic factor [Jing S. et al. (1996) Cell 85, 1113-1124; Treanor J. J. et al. (1996) Nature 382, 80-83], a survival factor for several populations of central and peripheral neurons, including midbrain dopamine neurons [Lin L. F. et al. (1993) Science 260, 1130-1132], and mediates its ligand-induced cell response via a tyrosine kinase receptor called Ret [Takahashi M. et al. (1988) Oncogene 3, 571-578; Takahashi M. and Cooper G. M. (1987) Molec. Cell Biol. 7, 1378-1385]. In this paper, we show that mice with a null mutation of the GFRalpha1 gene manifest epithelial-mesenchymal interaction deficits in kidney and severe disturbances of intestinal tract development similar to those seen with glial cell line-derived neurotrophic factor or Ret null mutations. There is a marked renal dysgenesis or agenesis and the intrinsic enteric nervous system fails completely to develop. We also show that newborn GFRalpha1-deficient mice display no or minimal changes in dorsal root and sympathetic ganglia. This is in contrast to the deficits reported in these neuronal populations in glial cell line-derived neurotrophic factor and Ret null mutations. Mesencephalic dopaminergic neurons in the substantia nigra and ventral tegmental area appear intact at the time of birth of the mutated mice. Mice homozygous for the GFRalpha1 null mutation die within 24 h of birth because of uremia. Heterozygous animals, however, live to adulthood. There is a significantly reduced neuroprotective effect of glial cell line-derived neurotrophic factor in such heterozygous animals, compared with wild-type littermates, after cerebral ischemia. Taken together with previous data on glial cell line-derived neurotrophic factor and Ret, our results strongly suggest that GFRalpha1 is the essential GFRalpha receptor for signaling in the glial cell line-derived neurotrophic factor-Ret pathway in the kidney and enteric nervous system development, and that GFRalpha2 or GFRalpha3 cannot substitute for the absence of GFRalpha1. Moreover, neuroprotective actions of exogenous glial cell line-derived neurotrophic factor also require full GFRalpha1 receptor expression.

Alleles↗
PubMed2000

Serotonergic modulation of ethanol-induced electrophysiological depression in young and aged rats.

BACKGROUND: Ethanol (EtOH)-induced electrophysiological depressions in cerebellar Purkinje neurons have been shown to be potentiated by exogenously applied serotonin (5HT). In this study, we determined whether this modulatory action can be activated by endogenous release from presynaptic serotonergic terminals, and whether such a response is altered by age or rat strain. METHODS: Extracellular 5HT levels in cerebellar cortex were measured in real time by in vivo chronoamperometry, by using Nafion-coated carbon fiber electrodes, in anesthetized young (3-5 months old) or aged (18-24 months old) Sprague Dawley and Fischer 344 rats. Some animals were prelesioned with 5,7 dihydroxytryptamine (5,7 DHT). Single unit electrophysiological activity was recorded from cerebellar Purkinje neurons. Serotonin or its presynaptic antagonist methiothepin was applied directly to cerebellar neurons through multibarrel pipettes. RESULTS: Local application of methiothepin dose-dependently induced 5HT overflow in young Sprague Dawley and Fisher 344 rats. Methiothepin-induced 5HT release was decreased significantly in aged or 5,7 DHT-lesioned rats. Local application of methiothepin or 5HT potentiated EtOH-induced electrophysiological depression of Purkinje neurons in young animals of both strains. Methiothepin-potentiated, EtOH-elicited neuronal inhibition was reduced greatly in aged or 5,7 DHT-lesioned rats. Serotonin-facilitated EtOH responses were reduced in the aged Sprague Dawley rats. CONCLUSIONS: EtOH-induced electrophysiological responses in cerebellum can be facilitated by endogenous 5HT release by using a 5HT autoreceptor antagonist. Such actions are attenuated in aged rats perhaps through a presynaptic serotonergic mechanism.

5,7-Dihydroxytryptamine↗
PubMed1999

A selective group of dopaminergic neurons express Nurr1 in the adult mouse brain.

Nurr1, an orphan receptor of the nuclear receptor superfamily, is widely expressed in the central nervous system (CNS) including brain regions where dopaminergic neurons are abundant. Recent analyses of Nurr1 null mutant mice have shown that Nurr1 is essential for the development and survival of midbrain dopaminergic neurons. However, other dopaminergic neuronal populations do not seem to be affected by ablation of the Nurr1 gene. The purpose of the present study was to investigate the degree of co-existence of Nurr1 mRNA and tyrosine hydroxylase (TH) immunoreactivity in the brain of adult mice to better characterize the selective effects of Nurr1 on catecholaminergic neurons. Our results indicate that the majority of TH-immunoreactive neurons in the substantia nigra (SN; 96%), ventral tegmental area (VTA; 95%), retrorubral field (91%), olfactory bulb (85%), linear nucleus raphe (91%) and central grey (61%) express Nurr1. In contrast, dopaminergic cells of the paraventricular and periventricular hypothalamic nucleus showed only a few Nurr1/TH double labeled neurons, while TH-immunoreactive neurons in the arcuate nucleus and zona incerta did not express Nurr1 mRNA. Nurr1 expression was also excluded from (nor)adrenergic neurons of the brainstem. In conclusion, Nurr1 transcripts were not found in all CNS catecholaminergic neurons. Nurr1 expression was confined to periglomerular and midbrain dopaminergic neurons. These results suggest that within the adult mouse brain, Nurr1 may participate in dopaminergic functions of the olfactory bulb and midbrain.

Animals↗
PubMed1999

Transplantation of fetal kidney tissue reduces cerebral infarction induced by middle cerebral artery ligation.

The authors, and others, have recently reported that intracerebral administration of glial cell line-derived neurotrophic factor (GDNF) or osteogenic protein-1 protects against ischemia-induced injury in the cerebral cortex of adult rats. Because these trophic factors are highly expressed in the fetal, but not adult, kidney cortex, the possibility that transplantation of fetal kidney tissue could serve as a cellular reservoir for such molecules and protect against ischemic injury in cerebral cortex was examined. Fetal kidneys obtained from rat embryos at gestational day 16, and adult kidney cortex, were dissected and cut into small pieces. Adult male Sprague-Dawley rats were anesthetized with chloral hydrate and placed in a stereotactic apparatus. Kidney tissues were transplanted into three cortical areas adjacent to the right middle cerebral artery (MCA). Thirty minutes after grafting, the right MCA was transiently ligated for 90 minutes. Twenty-four hours after the onset of reperfusion, animals were evaluated behaviorally. It was found that the stroke animals that received adult kidney transplantation developed motor imbalance. However, animals that received fetal kidney grafts showed significant behavioral improvement. Animals were later sacrificed and brains were removed for triphenyltetrazolium chloride staining, Pax-2 immunostaining, and GDNF mRNA expression. It was noted that transplantation of fetal kidney but not adult kidney tissue greatly reduced the volume of infarction in the cerebral cortex. Fetal kidney grafts showed Pax-2 immunoreactivity and GDNF mRNA in the host cerebral cortex. In contrast, GDNF mRNA expression was not found in the adult kidney grafts. Taken together, our data indicate that fetal kidney transplantation reduces ischemia/reperfusion-induced cortical infarction and behavioral deficits in adult rats, and that such tissue grafts could serve as an unique cellular reservoir for trophic factor application to the brain.

Animals↗
PubMed1999

Osteogenic protein-1 protects against cerebral infarction induced by MCA ligation in adult rats.

BACKGROUND AND PURPOSE: Osteogenic protein-1 (OP1) not only possesses trophic activity on bone tissue but also influences neuronal survival and differentiation in vitro. Specific receptors for OP1 are present in brain and spinal cord and can be upregulated during cerebral contusion. OP1 is a member of the transforming growth factor-beta superfamily, several of whose members possess neuroprotective activity. In this study, the neuroprotective effect of OP1 in cerebral ischemia was evaluated in adult animals. METHODS: Adult male Sprague-Dawley rats were anesthetized with chloral hydrate. OP1 or vehicle was administered intracortically or intracerebroventricularly to the rats. Thirty minutes, 24 hours, or 72 hours after OP1 injection, the right middle cerebral artery (MCA) was ligated for 90 minutes. Twenty-four hours after reperfusion, animals were tested for motor behavior. The animals were subsequently anesthetized with urethane and perfused intracardially with saline. Brain tissue was removed, sliced, and incubated with 2% triphenyltetrazolium chloride to localize the area of infarction. RESULTS: Only animals pretreated with OP1 24 hours before MCA ligation showed a reduction in motor impairment. OP1, given 30 minutes or 72 hours before MCA ligation, did not reduce cortical infarction. In contrast, pretreatment with OP1 24 hours before MCA ligation significantly attenuated the volume of infarction in the cortex, in agreement with the behavioral findings. CONCLUSIONS: Intracerebral administration of OP1 24 hours before MCA ligation reduces ischemia-induced injury in the cerebral cortex.

Animals↗
PubMed1998

In vivo electrochemical studies of dopamine clearance in subregions of rat nucleus accumbens: differential properties of the core and shell.

The dopamine (DA) uptake/clearance properties of the DA transporter (DAT) in the core and shell of the nucleus accumbens were measured using in vivo electrochemical recordings. Calibrated amounts of a DA solution were pressure-ejected from a micropipette/electrode assembly placed in the core or shell of the nucleus accumbens in anesthetized male Fischer 344 rats. Initial studies in the two brain regions revealed that the core and shell have different DA clearance properties as measured by the extracellular DA signal amplitudes, clearance times, and clearance rates. Although the same number of picomoles of DA were applied, DA clearance signals recorded in shell had significantly greater amplitudes but faster clearance rates than those recorded in the core. Systemic administration of 20 mg/kg cocaine, a monoamine transporter inhibitor, greatly increased the signal amplitude from the locally applied DA in both the core and shell. Signal amplitudes were increased to a greater extent in the shell, compared with the core, after cocaine administration. However, cocaine affected the clearance time of DA only in the core and the DA clearance rate only in the shell. Taken together with previously reported data, these studies further support differential activity of the DAT in the core versus shell subregions of the nucleus accumbens. In addition, these data indicate that DATs are more sensitive to the effects of psychomotor stimulants, such as cocaine, in the shell of the nucleus accumbens.

Animals↗
PubMed1998

Dopamine D1 and D2 receptor-mediated acute and long-lasting behavioral effects of glial cell line-derived neurotrophic factor administered into the striatum.

To determine the differences in behavioral effects between intrastriatal and intracerebroventricular glial cell-derived neurotrophic factor (GDNF) administration, spontaneous locomotor activity was measured after intrastriatal or intracerebroventricular injection of GDNF (10 microg) in normal adult rats with implanted guide cannulae. In addition, the distribution of GDNF after intracerebral injection was studied immunohistochemically. Intrastriatal administration of GDNF significantly increased rearing behavior 3-4 h after injection. Increases in all three aspects of locomotor activity (motility, locomotion, and rearing) were most pronounced 3 days after intrastriatal injection, and they lasted for several days. This hyperactivity was blocked by the selective dopamine D1 receptor antagonist SCH22390 and by the selective D2 receptor antagonist raclopride at doses of the dopamine receptor antagonists, which by themselves did not affect spontaneous locomotor activity. These results suggest that GDNF has both acute and long-lasting pharmacological effects on dopamine neurons in adult animals and stimulates locomotor activity by activating both dopamine D1 and D2 receptors. On the other hand, intracerebroventricular administration of the same dose of GDNF failed to increase locomotor activity at any time during the test period (12 days). The immunohistochemical study demonstrated widespread distribution of GDNF in the entire body of the striatum within 24 h after intrastriatal injection. It also revealed deep penetration of GDNF from the ventricular space into the brain parenchyma after intracerebroventricular injection. GDNF-immunoreactive neuronal cell bodies were seen in the ipsilateral substantia nigra pars compacta most frequently 6 h after intrastriatal injection. The number of such cell bodies after intracerebroventricular administration, on the other hand, was much lower than that seen after intrastriatal administration. Taken together, these data suggest that intrastriatal administration of GDNF is an effective approach for affecting DA transmission. Long-lasting behavior effects are mediated via dopamine D1 and D2 receptors. Higher doses of GDNF would probably be needed using the intracerebroventricular route as compared to intraparenchymal delivery to exert effects on the nigrostriatal system in Parkinson's disease patients.

Animals↗
PubMed1998

Intranigral ventral mesencephalic grafts and nigrostriatal injections of glial cell line-derived neurotrophic factor restore dopamine release in the striatum of 6-hydroxydopamine-lesioned rats.

We have previously reported that grafting of fetal ventral mesencephalic (VM) tissue to the nigral region of unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats, in conjunction with glial cell line-derived neurotrophic factor (GDNF) injection between nigra and striatum, restores nigrostriatal tyrosine hydroxylase (TH) immunoreactivity. In this study, we investigated the electrochemical indices of dopamine (DA) release in these grafted animals in the striatum and nigra. Adult Sprague-Dawley rats were anesthetized and unilaterally injected with 6-OHDA into the medial forebrain bundle. The completeness of lesions was tested by measuring methamphetamine-induced rotations. One to two months after 6-OHDA administration, fetal VM tissues were grafted in the lesioned nigral area followed by injection of GDNF, brain-derived neurotrophic factor (BDNF), or phosphate-buffered saline (PBS), along a tract from nigra to striatum. Animals receiving transplantation and GDNF, but not BDNF or PBS, injection showed a significant decrease in rotation 1-3 months after grafting. High-speed chronoamperometric recording techniques, using Nafion-coated carbon fiber electrodes, were used to evaluate DA overflow in the striatum. We found that 6-OHDA lesions resulted in a loss of KCl-induced DA overflow in the urethane-anesthetized rats. Three months after GDNF-bridged grafting, application of KCl elicited DA release both in nigra and striatum. The KCl-evoked DA release area was limited to the GDNF-bridging tract in the striatum. On the other hand, KCl did not induce DA release in the BDNF- or PBS-bridged grafts. Immunocytochemical studies indicated that TH-positive neurons and fibers were found in the nigra and striatum after GDNF-bridged grafting. Taken together, our data suggest that fetal nigral transplantation and GDNF injection may restore the nigrostriatal DA pathway and DA release in these hemiparkinsonian animals and support the hypothesis of trophic activity of GDNF on fiber outgrowth from midbrain DA neurons.

Animals↗
PubMed1998

On CNS repair and protection strategies: novel approaches with implications for spinal cord injury and Parkinson's disease.

In the adult mammalian central nervous system lost nerve cells are not replaced and there is no regeneration of injured axons in white matter. Together, these two facts mean that there are no spontaneous reparative mechanisms in operation. Instead, the adult central nervous system copes with the risks of injuries and diseases by protective encapsulation in bone, by a multitude of neuroprotective mechanisms, and finally by the fact that many important functions are represented by a much larger number of neurons than minimally needed. The long life expectancy of a human being nevertheless means that the risk that the central nervous system is affected by disease, injury or other forms of insults for which it cannot fully compensate is relatively high. Experimentally, two strategies are being pursued in order to develop ways of minimizing various forms of CNS damage, namely neuroprotective and reparative strategies. Here we present a possible reparative intervention applicable to spinal cord injury based on multiple white-to-gray matter peripheral nerve bridge grafts and work based on the specific role of Nurr1 for dopamine neuron development, suggesting that development of ligands to transcription factor might be a new inroad to neuroprotective treatments in Parkinson's disease.

Adult↗
PubMed1997

Carrier mediated delivery of NGF: alterations in basal forebrain neurons in aged rats revealed using antibodies against low and high affinity NGF receptors.

The distribution of low and high affinity nerve growth factor (NGF) receptors was investigated in the basal forebrain during aging and NGF treatment. A peripheral administration model for NGF was utilized. NGF was conjugated to a transferrin receptor antibody (OX-26-NGF), and this conjugate was injected into the tail vein of aged Fischer 344 male rats (24 months) twice weekly for 5 weeks (equivalent to 50 microg of NGF/injection). Controls were injected with a non-conjugated mixture of OX-26 and NGF. The aged rats treated with conjugate showed a significant increase in cell size of p75- and trkA-immunoreactive neurons in the medial septal nucleus and vertical limb of the diagonal band as compared to controls. A significant increase in cell size of trkA-immunoreactive neurons was also observed in the horizontal limb of the diagonal band in rats treated with conjugate. Rats treated with conjugate also showed a significant increase in overall staining density for p75 and trkA antibodies in the medial septal nucleus as compared to controls. A significant increase in staining density of p75-immunoreactive structures was also observed in the vertical and horizontal limbs of the diagonal band. Therefore, treatment with OX-26-NGF conjugate has regional effects on both the low and high affinity NGF receptors in terms of cell body size and staining density in the basal forebrain of aged rats. The current findings support the idea that this delivery system might be useful in therapeutic approaches involving the delivery of neurotrophic factors and other large molecules into the brain.

Aging↗
PubMed1997

A non-invasive transport system for GDNF across the blood-brain barrier.

Glial cell line-derived neurotrophic factor (GDNF) is a neurotrophin which supports midbrain dopaminergic neurons and spinal cord motorneurons. GDNF has been proposed as a possible therapeutic agent for Parkinson's disease, spinal cord injury or motorneuron degenerative disorders. Administration of GDNF is complicated by its poor penetration across the blood-brain barrier (BBB). Central nervous system capillaries are uniquely enriched in transferrin receptors and antibodies to these receptors (OX-26) have been proposed as potential carriers to transport large molecules across the BBB. Intravenous administration of an OX-26-GDNF conjugate enhanced survival of spinal cord motorneurons in intraocular transplants, which possess an organotypic BBB. This suggests that the OX-26-GDNF conjugate could be utilized for non-invasive treatment of neurodegenerative diseases of the spinal cord or midbrain dopaminergic neurons.

Animals↗
PubMed1997

Glial cell line-derived neurotrophic factor protects against ischemia-induced injury in the cerebral cortex.

Glial cell line-derived neurotrophic factor (GDNF), a recently described and cloned member of the transforming growth factor (TGF)-beta superfamily, has been shown to have marked trophic activity on several populations of central neurons. Survival-promoting and injury protectant activity in vitro and in vivo, using several paradigms, has been demonstrated for ventral mesencephalic dopaminergic neurons and spinal cord motoneurons. In view of a proposed commonality of mechanisms, involving intracellular free radical generation, depolarization-induced Ca2+ influx, and mitochondrial respiratory enzyme injury, between such GDNF-responsive paradigms and those of ischemia-induced injury, we tested the effects of GDNF on the extent of neural degeneration induced by transient middle cerebral artery (MCA) occlusion. We now report that intracerebroventricular and intraparenchymal administration of GDNF potently protects the cerebral hemispheres from damage induced by MCA occlusion. In addition, the increase in nitric oxide that accompanies MCA occlusion and subsequent reperfusion is blocked almost completely by GDNF. Thus, this protein may play an important role in the treatment of cerebrovascular occlusive disease.

Age Factors↗
PubMed1997

Dopamine neuron agenesis in Nurr1-deficient mice.

Dopamine neurons of the substantia nigra and ventral tegmental area regulate movement and affective behavior and degenerate in Parkinson's disease. The orphan nuclear receptor Nurr1 was shown to be expressed in developing dopamine neurons before the appearance of known phenotypic markers for these cells. Mice lacking Nurr1 failed to generate midbrain dopaminergic neurons, were hypoactive, and died soon after birth. Nurr1 expression continued into adulthood, and brains of heterozygous animals, otherwise apparently healthy, contained reduced dopamine levels. These results suggest that putative Nurr1 ligands may be useful for treatment of Parkinson's disease and other disorders of midbrain dopamine circuitry.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1997

Morphological alterations in the peripheral and central nervous systems of mice lacking glial cell line-derived neurotrophic factor (GDNF): immunohistochemical studies.

Glial cell line-derived neurotrophic factor (GDNF) is a member of the TGF-beta superfamily of growth factors with neurotrophic activity on midbrain dopaminergic neurons and on developing and mature motoneurons of the brainstem and spinal cord. To investigate the extent of GDNF dependency of central and peripheral nervous structures during development, we have performed an immunohistochemical analysis of sections from the whole head including brain, peripheral ganglia, developing teeth and tongue, as well as intestines, in mutant mice lacking a part of the third exon that encodes the GDNF protein. As described previously, these null-mutated mice lack most of the enteric nerve plexus and are subject to agenesis or severe dysgenesis of the kidneys. In the present communication, we examined the development of vibrissae and incisor and molar teeth, as well as the innervation of these structures, and found no differences between null-mutated and control mice. A decrease in the immunohistochemical labeling intensity with tyrosine hydroxylase was observed in the superior cervical ganglion (SCG), as well as in the pontine nucleus locus coeruleus, and the sympathetic innervation of blood vessels and glands in the head was significantly decreased. None of the brain nuclei studied exhibited any significant decreases in the total number of neurons, but the packing density of neurons in the nucleus locus coeruleus was decreased. These data indicate that GDNF might be one neurotrophic factor that contributes to the development of central and peripheral noradrenergic neurons.

Animals↗
PubMed1997

Platelet mitochondrial respiratory chain function in Parkinson's disease.

Reports on mitochondrial respiratory chain (MRC) complex I (CI) dysfunction in the substantia nigra in Parkinson's disease (PD) support the oxidative stress hypothesis in the neuropathogenesis of PD. Studies in peripheral tissue have found variable decreased CI and occasionally other complex activity suggestive of systemic impairment of MRC function in PD; however, MRC activity may be influenced by numerous variables. We conducted spectrophotometric measurements of MRC function in platelet mitochondrial preparations in 13 individuals with PD and 9 age-matched controls (CON) and have identified additional variables that may affect MRC activity. Mean CI, CIII, CIV, and citrate synthase (CS) activities were similar between PD and CON. CIII and CIV, specific and CS-corrected, activities were significantly positively correlated with CI in combined and individual group data, with the exception of CIII CS-corrected and CIV specific activities in CON and PD, respectively. CIII and CS specific activities were negatively correlated with age in CON, but varied randomly in PD. In PD, CIII specific activity was 1.4-fold higher in those with a history of environmental risk factors for PD and CIV specific activity was lower in those with a positive family history of PD [8.34 +/- 0.74 (n = 4) vs. 12.4 +/- 1.1 (SEM) min-1 mg-1; p = 0.046]. Group heterogeneity, variables affecting enzyme activity, and intrinsic properties of cells may thus contribute to conflicting data in studies of MRC function in platelets and other tissues.

Adult↗