Altered expression of synaptic protein mRNAs in STOP (MAP6) mutant mice

Abstract

proteins, was quantified in female STOP null (n=7), heterozygous (n=5) and wild type (n=6) mice. For STOP null and heterozygous mice, synaptophysin, VGlut1, GAP-43 and spinophilin mRNAs were decreased in the hippocampus, whilst in addition in the null mice, synaptophysin, VGlut1 and spinophilin mRNAs were decreased in the cerebellum. Alterations in synaptic protein mRNA expression were also detected in the frontal and occipital cortex.MAP2 mRNA expression was unchanged in all brain regions. The profile of mRNA changes is broadly similar to that observed in schizophrenia. Together the data provide supporting evidence for a role for microtubules in synaptic function, and suggest that STOP, or other microtubule proteins, may contribute to the synaptic pathology of schizophrenia.

Nitric Oxide Synthase Mediates the Ability of Darbepoetin Alfa to Improve the Cognitive Performance of STOP Null Mice

“…The Map6 gene product known as STOP (stable tubule only peptide) is a Ca 2 + -calmodulin regulated microtubule-associated protein present in neurons, oligodendrocytes, and astrocytes (Bosc et al, 2003;Denarier et al, 1998;Galiano et al, 2004). Mice lacking a functional copy of STOP (STOP null) display several synaptic abnormalities that are accompanied by an array of cognitive deficits (Begou et al, 2008;Brun et al, 2005;Eastwood et al, 2007;Powell et al, 2007). STOP null mice display a two-fold reduction in pre-synaptic glutamatergic vesicle density in the CA1 region of the hippocampus, a brain structure implicated in learning and memory (Andrieux et al, 2002).…”

Chronic administration of atypical antipsychotics improves behavioral and synaptic defects of STOP null mice

“…Hence, STOP null mice exhibit both short-and long-term synaptic plasticity defects in the hippocampus (Andrieux et al 2002) associated with depleted glutamatergic vesicle pools. Moreover, levels of mRNAs encoding synaptic proteins, such as synaptophysin, growth-associated protein-43, and spinophilin, are decreased in specific hippocampic subregions (Eastwood et al 2007).…”

Chronic intermittent hypoxia induces changes in expression of synaptic proteins in the nucleus of the solitary tract

“…Synaptophysin is a marker for synapses and synaptic strength, and has been used for the quantification of synapses (Calhoun et al, 1996). On the other hand, GAP-43 is an important mediator of neurite outgrowth (Jap Tjoen San et al, 1991), neuronal regeneration (Meiri et al, 1988) and a marker of the presynaptic terminals (Eastwood et al, 2007). Consistent with the findings in this study, it has recently been shown that CIH exposure reduces afferent neurotransmission in the intermediate and caudal NTS (Almado et al, 2012).…”