Lipid Classes and Fatty Acid Patterns are Altered in the Brain of γ-Synuclein Null Mutant Mice

The well-documented link between α-synuclein and the pathology of common human neurodegenerative diseases has increased attention to the synuclein protein family. The involvement of α-synuclein in lipid metabolism in both normal and diseased nervous system has been shown by many research groups. However, the possible involvement of γ-synuclein, a closely-related member of the synuclein family, in these processes has hardly been addressed. In this study, the effect of γ-synuclein deficiency on the lipid composition and fatty acid patterns of individual lipids from two brain regions has been studied using a mouse model. The level of phosphatidylserine (PtdSer) was increased in the midbrain whereas no changes in the relative proportions of membrane polar lipids were observed in the cortex of γ-synuclein-deficient compared to wild-type (WT) mice. In addition, higher levels of docosahexaenoic acid were found in PtdSer and phosphatidylethanolamine (PtdEtn) from the cerebral cortex of γ-synuclein null mutant mice. These findings show that γ-synuclein deficiency leads to alterations in the lipid profile in brain tissues and suggest that this protein, like α-synuclein, might affect neuronal function via modulation of lipid metabolism

Parkinson's Disease: Basic Pathomechanisms and a Clinical Overview

PD is a common and a debilitating degenerative movement disorder. The number of patients is increasing worldwide and as yet there is no cure for the disease. The majority of existing treatments target motor symptom control. Over the last two decades the impact of the genetic contribution to PD has been appreciated. Significant discoveries have been made, which have advanced our understanding of the pathophysiological and molecular basis of PD. In this chapter we outline current knowledge of the clinical aspects of PD and the basic mechanistic understanding

Evaluation of the cholinergic hypothesis in Alzheimer's disease with neuropsychological methods

This study aimed at evaluating the cholinergic hypothesis in Alzheimer's disease (AD) patients utilizing the pupillometry method, cognitive tests and Hamilton Depression Rating Scale (HAM-D), as well as to examine whether a correlation between cognitive tests and pupillometry exists. Forty-two patients with mean age 69.2 +/- A 7.0 years and documented AD volunteered to participate in this study, while 33 healthy matched subjects served as controls. All subjects underwent a pupillometric measurement and performed the Wechsler Memory Scale (WMS) and Mini Mental State Examination (MMSE). Also, HAM-D was used to assess the severity of depressive symptoms. The pupillometric parameters studied were (1) latency for the onset of constriction (T1), (2) maximum constriction velocity (VCmax), and (3) maximum constriction acceleration (ACmax). In AD patients MMSE and WMS score were correlated with ACmax (r = -0.409, p < 0.05 and r = -0.513, p < 0.05, respectively) and VCmax (r = -0.664, p < 0.05 and r = -0.771, p < 0.05), respectively. Moreover, T1 was found to be significantly increased by 23 % (p < 0.05) in AD patients compared to healthy subjects. Conversely, the mean scores of VCmax and ACmax were significantly decreased in AD patients by 46 % (p < 0.05) and by 47 % (p < 0.05), respectively, as compared to healthy subjects. There was no significant difference between the two groups for HAM-D. Additionally, AD patients showed decreased score in WMS by 40 % (p < 0.05) and in MMSE by 28.5 % (p < 0.05) compared to healthy subjects. Of the indices that were studied VCmax and ACmax are governed mainly by the action of the Parasympathetic Nervous System. The results of this study demonstrated that there is a correlation between cognitive tests and pupillometry in AD patients. Thus, pupillometry could be considered as a sensitive technique for the investigation of cholinergic deficits, which indirectly lead to memory and cognitive disorders in AD patients