Abstract

During cerebellar development, granule cell precursors are produced from a secondary germinative zone forming the external granule cell layer (EGL). Immature granule neurons from the inner part of the EGL then start a tangential migration followed by a centripetal inward radial migration across the molecular and Purkinje cell layers to reach their final destination at the bottom of the forming internal granule cell layer (IGL). This complex migratory process is highly regulated and takes about 2 days in rodents and it is essential for the proper formation of the cortical layers forming the mature cerebellum. In the IGL, granule cells differentiate to establish functional excitatory synapses with GABAergic neurons including Purkinje, basket, stellate and Golgi cells, or die. Some neurotrophins and neurotransmitters have been shown to be involved in the control of cerebellar granule cell survival, migration and differentiation. Initially, when I started my carrier as a researcher, we used to claim that very few neuropeptides were produced in the cerebellum. Nevertheless, we now know that this was wrong as we have recently identified by mass spectrometry over 70 peptides expressed in the cerebellum during development. Over the years, the involvement of some of these peptides such as somatostatin, PACAP or ODN, has been established in the control of cerebellar granule cell survival, migration and differentiation as will illustrate my presentation.

Highlights

  • Alzheimer’s disease (AD) is an incurable neurodegenerative disease characterized by progressive dementia

  • The results of the present study indicate that development of the neuronal hypoxic tolerance induced by the three-trial, in contrast to one-trial, mild hypoxic preconditioning is apparently largely associated with the activation of CREB, as well as brain-derived neurotrophic factor (BDNF) and Bcl-2 overexpression

  • No significant differences in serum level of Solubile form of RAGE (sRAGE) where found between rapidly progressing and slow progressing subgroup of multiple sclerosis (MS) patients.Our results suggest for the role of sRAGE in MS ethiopathogenesis, but we did not find any association of sRAGE in serum with the rate of MS disability progression

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Summary

Introduction

Alzheimer’s disease (AD) is an incurable neurodegenerative disease characterized by progressive dementia. The aim of the study was to characterize the effects of streptozocin (STZ)-indced diabetes on learning and memory of 5XFAD and wild-type (WT) mice in Morris water maze (MWM) at ages 2 and 6 months and on brain amyloid load. Existing evidence suggests GABAergic system is involved in pathophysiology of Alzheimer’s disease (AD) via inhibitory interneuron deficits (Verret et al, 2012) and decrease in functional GABAA receptors (Limon et al, 2012). Our concept: low doses of muscimol may prevent learning/memory deficits in intracerebroventricular (icv) streptozocin (STZ)-induced AD nontransgenic rat model. The Sigma-1 receptor is a chaperone protein that modulates intracellular calcium signalling of the endoplasmatic reticulum and is involved in learning and memory processes.The aim of the present study was to compare in vitro Ca2+ concentration modulating activity and in vivo behavioural effects of enantiomers of methylphenylpiracetam, a novel positive allosteric modulator of Sigma-1 receptors

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