Biomedical subjects

Yiwen Zheng

Publications and source records attributed to Yiwen Zheng.

13 recordsLinked to original sources

PubMed2006

Neuronal nitric oxide synthase expression in the cochlear nucleus in a salicylate model of tinnitus.

Although a number of studies suggest that the development of tinnitus is associated with hyperactive neuronal discharges in the brainstem cochlear nucleus (CN), there is relatively little evidence to indicate the neurochemical basis of this phenomenon. While some studies suggest that it may be partly due to a decrease in GABAergic inhibition, it is also possible that increased excitability is a contributing factor. In the current study, we investigated whether the salicylate animal model of tinnitus is associated with changes in the number of CN neurons expressing neuronal nitric oxide synthase (nNOS), one of the NOS isoforms that results in the production of the neurotransmitter, nitric oxide. We used a behavioral conditioning paradigm to confirm that animals receiving salicylate injections experienced tinnitus, and used immunohistochemistry with stereology to quantify the number of nNOS-expressing neurons in the dorsal and ventral CN (DCN and VCN, respectively) in salicylate- and vehicle control-treated animals. We also employed Western blotting to quantify the amount of nNOS protein expression in the total CN (i.e., the DCN and VCN together). We found a significant increase (of approximately 70%) in the number of nNOS-expressing principal neurons in the VCN of salicylate-treated animals compared to controls, with no significant differences in the DCN; nor did we find any significant difference in the overall level of nNOS protein in the total CN using Western blotting. These results suggest that changes in the number of neurons in the VCN expressing nNOS may be implicated in the mechanisms of tinnitus.

Animals↗

PubMed2006

Impairment and recovery on a food foraging task following unilateral vestibular deafferentation in rats.

It has been suggested that the vestibular system may contribute to the development of higher cognitive function, especially spatial learning and memory that uses idiothetic cues (e.g., dead reckoning). However, few studies have been done using behavioral tasks that could potentially separate the animals' ability for dead reckoning from piloting. The food foraging task requires the animal to continuously monitor and integrate self-movement cues and generate an accurate return path. It has been shown that bilateral vestibular-lesioned rats were impaired on this task. The present study used the same task to further examine the contribution of vestibular information to spatial navigation by comparing unilateral and bilateral lesions and by testing the animals at different time points following the lesion. The results demonstrated that animals with unilateral vestibular deafferentation were impaired in performing the task in the dark at 3 months after the lesion, and this impairment disappeared at 6 months after the lesion. This supports the notion that vestibular information contributes to dead reckoning and suggests possible recovery of function over time after the lesion. Animals with bilateral vestibular deafferentation were not able to be tested on the foraging task because they exhibited behavior distinct from the unilateral-lesioned animals, with significant hesitation in leaving their home cage for as long as 6 months after the lesion.

Animals↗

PubMed2005

Ginkgo biloba extracts for tinnitus: More hype than hope?

The investigation into the effects of Ginkgo biloba extracts on tinnitus has suffered from a dearth of effective animal models as well as systematic clinical trials employing double-blind and placebo-controlled designs. Some clinical trials have yielded positive results, however, these studies are few and have been limited either by design flaws, the small size of the significant effects, or else the results have not been published in peer-reviewed journals and therefore the quality of the research is not assured. By contrast, the two most systematic clinical trials, both double-blind and placebo controlled, and published in respected peer-reviewed journals, have yielded negative results and suggest that Ginkgo biloba extracts are of little more use in the treatment of tinnitus than a placebo. Treatments for tinnitus that do not have therapeutic efficacy not only waste money but can potentially prevent patients from seeking therapy that is efficacious. Furthermore, the unsupervised use of Ginkgo biloba extracts with other medications could lead to adverse side effects which are unnecessary and not justified in terms of therapeutic benefit.

Ginkgo biloba↗

PubMed2005

The effects of vestibular lesions on hippocampal function in rats.

Interest in interaction between the vestibular system and the hippocampus was stimulated by evidence that peripheral vestibular lesions could impair performance in learning and memory tasks requiring spatial information processing. By the 1990s, electrophysiological data were emerging that the brainstem vestibular nucleus complex (VNC) and the hippocampus were connected polysynaptically and that hippocampal place cells could respond to vestibular stimulation. The aim of this review is to summarise and critically evaluate research published in the last 5 years that has seen major progress in understanding the effects of vestibular damage on the hippocampus. In addition to new behavioural studies demonstrating that animals with vestibular lesions exhibit impairments in spatial memory tasks, electrophysiological studies have confirmed long-latency, polysynaptic pathways between the VNC and the hippocampus. Peripheral vestibular lesions have been shown to cause long-term changes in place cell function, hippocampal EEG activity and even CA1 field potentials in brain slices maintained in vitro. During the same period, neurochemical investigations have shown that some hippocampal subregions exhibit long-term changes in the expression of neuronal nitric oxide synthase, arginase I and II, and the NR1 and NR2A N-methyl-D-aspartate (NMDA) receptor subunits following peripheral vestibular damage. Despite the progress, a number of important issues remain to be resolved, such as the possible contribution of auditory damage associated with vestibular lesions, to the hippocampal effects observed. Furthermore, although these studies demonstrate that damage to the vestibular system does have a long-term impact on the electrophysiological and neurochemical function of the hippocampus, they do not indicate precisely how vestibular information might be used in hippocampal functions such as developing spatial representations of the environment. Understanding this will require detailed electrical stimulation and lesion studies to elucidate the way in which different kinds of vestibular information are transmitted to various hippocampal subregions.

Animals↗

PubMed2005

Does vestibular damage cause cognitive dysfunction in humans?

For more than a decade, evidence from animal studies has suggested that damage to the vestibular system leads to deficits in spatial navigation which are indicative of impaired spatial learning and memory. More recently, direct evidence has emerged to demonstrate that humans with vestibular disorders exhibit a range of cognitive deficits that are not just spatial in nature, but also include non-spatial functions such as object recognition memory. Vestibular dysfunction has been shown to adversely affect attentional processes and increased attentional demands can worsen the postural sway associated with vestibular disorders. Recent MRI studies also show that humans with bilateral vestibular damage undergo atrophy of the hippocampus which correlates with their degree of impairment on spatial memory tasks. These results are consistent with those from animal studies and, together, suggest that humans with vestibular disorders are likely to experience cognitive dysfunction which is not necessarily related to any particular episode of vertigo or dizziness, and therefore may occur even in patients who are otherwise well compensated. These findings may be related to the observation that patients with vestibular deficits experience a high incidence of depression and anxiety disorders.

Animals↗

PubMed2004

Cytosolic glucocorticoid receptor expression in the rat vestibular nucleus and hippocampus following unilateral vestibular deafferentation.

It has been suggested that vestibular compensation, the process of behavioural recovery that occurs following peripheral vestibular damage, might be partially dependent on the release of glucocorticoids (GC) during the early stages of recovery from the lesion. One possibility is that glucocorticoid receptors (GRs) in the vestibular nucleus complex (VNC) might change following the lesion, altering their response to GCs. We sought to test this hypothesis by quantifying the expression of cytosolic GRs in the bilateral VNCs at 10 h, 58 h and 2 weeks following unilateral vestibular deafferentation (UVD) in rat, using western blotting. We also examined GR expression in the CA1, CA2/3 and dentate gyrus (DG) subregions of the hippocampus and measured serum corticosterone levels. Compared with sham surgery and anaesthetic controls, we found no significant changes in GR expression in the ipsilateral or contralateral VNCs at any time post-UVD. However, we did find a significant decrease in GR expression in the ipsilateral CA1 at 2 weeks post-UVD. Serum corticosterone levels were significantly lower in all groups at 58 h post-op. compared to 10 h and 2 weeks; however, there were no significant differences between the UVD and control groups at any time point. These results suggest that changes in GR expression in the VNC are unlikely to contribute to the development of vestibular compensation. However, long-term changes in GR expression in CA1 might be related to chronic deficits in hippocampal function and spatial cognition following vestibular damage.

Adaptation, Physiological↗

PubMed2004

Immunohistochemical characterisation and localisation of cannabinoid CB1 receptor protein in the rat vestibular nucleus complex and the effects of unilateral vestibular deafferentation.

CB1 receptor expression has been reported to be low in the brainstem compared with the forebrain, and low in the vestibular nucleus complex (VNC) compared with other regions in the brainstem. However, a frequent effect of cannabis is dizziness and loss of balance. This may be due to the activation of cannabinoid receptors in the central vestibular pathways. We used immunohistochemistry to study the distribution of CB1 receptor protein in the VNC, and Western blotting to measure CB1 receptor expression in the VNC following unilateral vestibular deafferentation (UVD); the hippocampal CA1, CA2/3 and dentate gyrus (DG) regions were also analysed for comparison. This study confirms a previous electrophysiological demonstration that CB1 receptors exist in significant densities in the VNC and are likely to contribute to the neurochemical control of the vestibular reflexes. Nonetheless, CB1 receptor expression did not change significantly in the VNC during vestibular compensation. In addition, despite some small but significant changes in CB1 receptor expression in the CA2/3 and the DG following UVD, in no case were these differences statistically significant in comparison to both control groups.

Animals↗

PubMed2004

Bilateral labyrinthectomy causes long-term deficit in object recognition in rat.

It has been reported that patients with vestibular disorders experience a wide range of cognitive disorders, including memory loss. However, to our knowledge, no study has investigated the contribution of vestibular information to episodic memory in experimental animals using vestibular deafferentation. In the present study, the effects of a complete unilateral or bilateral surgical lesion of the vestibular labyrinths in a spontaneous object recognition task were evaluated in Wistar rats 3 and 6 months following the surgery. We found that rats with bilateral vestibular deafferentation, but not those with unilateral vestibular deafferentation were impaired on the task at both time points. These results suggest for the first time that vestibular information may contribute to non-spatial memory to some extent.

Analysis of Variance↗

PubMed2003

Nitric oxide synthase and arginase expression in the vestibular nucleus and hippocampus following unilateral vestibular deafferentation in the rat.

The aim of this study was to investigate the possible relationship between changes in neuronal and endothelial nitric oxide synthase (nNOS and eNOS) and arginase expression in the vestibular nucleus complex and the hippocampus (CA1, CA2/3 and the dentate gyrus (DG) at 10 h or 2 weeks following a unilateral vestibular deafferentation (UVD) in rats. There were no significant differences in nNOS or arginase II expression in the ipsilateral or contralateral VNC at either 10 h or 2 weeks post-UVD. For eNOS, there was only a significant decrease in expression in the ipsilateral VNC at 2 weeks post-UVD (P<0.01). In the hippocampus, the only significant difference in nNOS expression was a decrease in the ipsilateral DG at 2 weeks post-UVD (P<0.05). There was a significant decrease in eNOS expression in the contralateral CA2/3 region at 10 h post-UVD (P<0.01). The only other significant change in eNOS was an increase in the contralateral DG at 10 h post-UVD (P<0.01). Although arginase II was expressed in all regions of the hippocampus, there were no significant differences in arginase II expression at any time point following UVD. These results suggest that the changes in NOS expression that occur in the VNC and hippocampus following UVD are not correlated with one another or with changes in arginase II.

Animals↗

PubMed2003

Adrenalectomy-induced cell death in the dentate gyrus: further characterisation using TUNEL and effects of the Ginkgo biloba extract, EGb 761, and ginkgolide B.

This study investigated the potential neuroprotective effects of the Ginkgo biloba extract, EGb-761, and ginkgolide B, on adrenalectomy (ADX)-induced cell death in the dentate gyrus (DG). Adrenalectomised, sham surgery-treated, and naive controls received either EGb-761 (25, 50, or 100 mg/kg), 0.9% saline vehicle control, ginkgolide B (10 or 25 mg/kg), or a polyethylene glycol vehicle control, i.p, daily for 6 days postsurgery. Cell death in the DG was determined by in situ labelling of DNA fragments, using the TUNEL method; sections were counterstained with hematoxylin. Radioimmunoassay was used to confirm a decrease in plasma corticosterone (CORT) after ADX. TUNEL-positive granule cells were observed in the DG at 1 week, but not at 24 h, post-ADX. The rate of granule cell death at this time was highest in the suprapyramidal blade and increased in a crest tip and a rostrotemporal gradient. Whereas CORT replacement completely prevented the occurrence of TUNEL-positive granule cells, EGb-761 and ginkgolide B did not, at any of the doses used. These results suggest that these drugs may not have substantial neuroprotective effects in the ADX model of neurodegeneration.

Adrenalectomy↗

PubMed2003

Changes in NOS protein expression and activity in the rat hippocampus, entorhinal and postrhinal cortices after unilateral electrolytic perirhinal cortex lesions.

The integrity of the perirhinal cortex is critical for certain types of learning and memory. One important issue relating to the function of this region is its interaction with other brain areas that play a role in memory processing. This study investigates the time course of changes in activity and protein expression of nitric oxide synthase (NOS), which transforms L-arginine into nitric oxide (NO) and citrulline, in the hippocampus and the entorhinal and postrhinal cortices after unilateral electrolytic lesions of the perirhinal cortex. Electrolytic lesions of the perirhinal cortex resulted in long lasting changes in NOS activity and protein expression in the entorhinal and postrhinal cortices (< or = 2 weeks post-lesion). In contrast, there was a small and transient decrease in nNOS expression (with no change in NOS activity) in the dorsal portion of the hippocampus. iNOS was not expressed in any region examined at any time point. These findings provide the first evidence that electrolytic lesions of the perirhinal cortex can result in long-term neurochemical changes in its anatomically related structures. Given that NO has been implicated in neuroplasticity processes, the interpretation of memory impairments induced by electrolytic lesions of the perirhinal cortex (and possibly, therefore, other brain regions) need to be considered with regard to these findings.

Animals↗

PubMed2003

Unilateral inner ear damage results in lasting changes in hippocampal CA1 field potentials in vitro.

We investigated the effects of a surgical lesion of one vestibular inner ear (unilateral vestibular damage [UVD]) on the field potential responses of CA1 neurons in vitro. Hippocampal slices were removed from rats at 4-6 weeks or 5-6 months post-UVD, and the field responses of CA1 neurons to electrical stimulation of the Schaffer collateral commissural pathway were analyzed. Compared with slices from sham and naive control animals, slices from UVD animals at 5-6 months post-UVD exhibited decreases in the population spike amplitude, the somal field excitatory postsynaptic potential (sfEPSP) slope, and the field EPSP (fEPSP) slope. For the population spike amplitude and fEPSP slope, this effect was observed in both CA1 ipsilateral and contralateral to the UVD. On both the ipsilateral and contralateral sides, paired-pulse testing showed increases in paired-pulse inhibition at the shortest interstimulus intervals (ISIs), with increases in paired-pulse facilitation at longer ISIs. This study provides the first evidence that peripheral vestibular damage can produce long-term changes in hippocampal electrophysiological activity in vitro.

Action Potentials↗

PubMed2002

NMDA and AMPA receptor subunit protein expression in the rat vestibular nucleus following unilateral labyrinthectomy.

We examined the expression of the NR1 and NR2A subunits of the N-methyl-D-aspartate (NMDA) receptor, and the GluR2 subunit of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor, in the ipsilateral and contralateral vestibular nucleus complexes (VNCs) at 10 h and 2 weeks following unilateral vestibular deafferentation (UVD) in rats, in order to directly test the hypothesis that the behavioural recovery following UVD ('vestibular compensation') is associated with an up-regulation of NMDA receptors. We found no significant changes in NR1 or NR2A expression at 10 hs or 2 weeks post-op. compared to sham and anesthetic controls. We did find a significant (p < 0.01 and p < 0.05) increase in GluR2 expression in both VNCs at 10 h but not 2 weeks post-op. compared to sham and anesthetic controls; however, comparison over time post-UVD failed to detect a significant difference, suggesting that it was small and transient at best. These results add further evidence to the conclusion that NMDA receptors do not undergo up-regulation in the ipsilateral VNC during vestibular compensation.

Animals↗