Synaptic protein expression in the medial temporal lobe and frontal cortex following chronic bilateral vestibular loss

Abstract

Several studies have reported that bilateral vestibular deafferentation (BVD) results in the disruption of place cell function and theta activity in the hippocampus. Recent magnetic resonance imaging (MRI) studies in humans demonstrated that bilateral but not unilateral vestibular loss is associated with a bilateral atrophy of the hippocampus. In this study we investigated whether BVD in rats resulted in changes in the expression of four proteins related to neuronal plasticity, synaptophysin, SNAP-25, drebrin and neurofilament-L, in the hippocampal subregions (CA1, CA2/3, the DG) and the entorhinal (EC), perirhinal (PRC) and frontal cortices (FC), using western blotting. At 6 months following BVD, there were no significant differences in the expression of synaptophysin in any region. There were also no significant differences in SNAP-25 expression in CA1, CA2/3, EC, PRC, or the FC; however, there was a significant increase in SNAP-25 expression in the DG compared to sham controls. Drebrin A and E expression was significantly reduced in the EC and drebrin A was significantly reduced in the FC of BVD animals. NF-L expression was not significantly different in CA1, CA2/3, DG, EC, or the PRC. However, its expression was significantly reduced in the FC of BVD animals. These data suggest that circumscribed neurochemical changes in SNAP-25, drebrin and NF-L expression occur in the DG, EC, and the FC over 6 months following BVD.

Balance before Reason in Rats and Humans

“…Our recent studies in rats have confirmed that BVD results in widespread apoptosis (i.e., “programmed cell death”) throughout the hippocampus (unpublished observations; see Fig. 4), which, along with changes in synaptic structure, 26 may account for the hippocampal atrophy observed in humans. On the other hand, unilateral vestibular deafferentation (UVD) in humans does not result in hippocampal atrophy or the same memory deficits as BVD 30 …”

“…Again, it is conceivable that auditory damage associated with peripheral vestibular lesions was partly responsible for the disruption of place‐cell firing; however, there is little evidence to date that auditory stimulation can modulate place‐cell activity in rats. Neurochemical studies have shown changes in the expression of nitric oxide synthase, 23,24 N ‐methyl‐ d ‐aspartate receptor subunits, 25 synaptosome‐associated protein of 25 kDa 26 (SNAP‐25), the serotonin transporter, 27 and tryptophan hydroxylase 27 in various subregions of the hippocampus following vestibular damage, but no change in synaptophysin, 26 drebrin, 26 neurofilament– l , 26 dopamine‐β‐hydroxylase, 27 the dopamine transporter, 27 tyrosine hydroxylase, 27 cannabinoid CB1 receptors, 28 or glucocorticoid receptors 29 . In a recent MRI study, Brandt and colleagues 8 reported that patients with BVD exhibited both spatial memory deficits and a bilateral hippocampal atrophy of approximately 17% (see Fig.…”

Move it or lose it—Is stimulation of the vestibular system necessary for normal spatial memory?

“…Neurochemical studies have shown changes in the expression of nitric oxide synthase (Zheng et al, 2001;Liu et al, 2003a), N-methyl-D-aspartate (NMDA) receptor subunits (Liu et al, 2003b), synaptosome-associated protein of 25 kDa (SNAP-25 0 ; Goddard et al, 2008b), the serotonin transporter (Goddard et al, 2008c), and tryptophan hydroxylase (Goddard et al, 2008c) in various subregions of the hippocampus following vestibular damage, with no change in synaptophysin, drebrin, neurofilament-L (Goddard et al, 2008b), dopamine-b-hydroxylase, the dopamine transporter, tyrosine hydroxylase (Goddard et al, 2008c), cannabinoid CB1 receptors (Ashton et al, 2004), or glucocortioid receptors (Lindsay et al, 2005). In a recent magnetic resonance imaging (MRI) study, Brandt et al (2005) reported that patients with bilateral vestibular loss exhibited both spatial memory deficits and a bilateral hippocampal atrophy of 17%.…”

Melatonin improves presynaptic protein, SNAP‐25, expression and dendritic spine density and enhances functional and electrophysiological recovery following transient focal cerebral ischemia in rats

“…Since melatonin also has the ability to boost a variety of neurotrophic factors [31–35], we proposed that it might work well as a treatment modality for enhancing neuroplasticity (the second option) during the subacute stage of stroke. Recent studies also indicate that neuronal differentiation is accompanied by increased levels of synaptosomal‐associated protein of 25 kDa (SNAP‐25) and synaptophysin (a calcium‐binding protein found on presynaptic vesicle membranes) proteins in neurons [36, 37]. In addition, dendritic spine density has been implicated to play an essential role in neuronal plasticity [38, 39].…”