Mitochondrial Protection and Against Glutamate Neurotoxicity via Shh/Ptch1 Signaling Pathway to Ameliorate Cognitive Dysfunction by Kaixin San in Multi-Infarct Dementia Rats

Multi-infarct dementia (MID), a prominent subtype of vascular dementia (VD), is responsible for at least 15 to 20 percent of dementia in the elderly. Mitochondrial dysfunctions and glutamate neurotoxicity due to chronic hypoperfusion and oxidative stress were regarded as the major risk factors in the pathogenesis. Kaixin San (KXS), a classic prescription of Beiji Qianjin Yaofang, was applied to treatment for “amnesia” and has been demonstrated to alleviate the cognitive deficit in a variety of dementias, including MID. However, little is known whether mitochondria and glutamate are associated with the protection of KXS in MID treatment. The aim of this study was to investigate the role of KXS in improving the cognitive function of MID rats through strengthening mitochondrial functions and antagonizing glutamate neurotoxicity via the Shh/Ptch1 signaling pathway. Our data showed that KXS significantly ameliorated memory impairment and hippocampal neuron damage in MID rats. Moreover, KXS improved hippocampal mitochondrial functions by reducing the degree of mitochondrial swelling, increasing the mitochondrial membrane potential (MMP), and elevating the energy charge (EC) and ATP content in MID rats. As expected, the concentration of glutamate and the expression of p-NMDAR1 were significantly reduced by KXS in the brain tissue of MID rats. Furthermore, our results showed that KXS noticeably activated the Shh/Ptch1 signaling pathway which was demonstrated by remarkable elevations of Ptch1, Smo, and Gli1 protein levels in the brain tissue of MID rats. Intriguingly, the inhibition of the Shh signaling pathway with cyclopamine significantly inhibited the protective effects of KXS on glutamate-induced neurotoxicity in PC12 cells. To sum up, these findings suggested that KXS protected MID rats from memory loss by rescuing mitochondrial functions as well as against glutamate neurotoxicity through activating Shh/Ptch1 signaling pathway.

The potential neuroprotective role of Amphora coffeaeformis algae against monosodium glutamate-induced neurotoxicity in adult albino rats

The current study provides a novel approach for treating monosodium glutamate neurotoxicity using safely cultivated Amphora coffeaeformis algae.

Synaptic Signals from Glutamate-Treated Neurons Induce Aberrant Post-Synaptic Signals in Untreated Neuronal Networks

Background and Objective: Glutamate neurotoxicity is associated with a wide range of disorders and can impair synaptic function. Failure to clear extracellular glutamate fosters additional cycles and spread of regional hyperexcitation. Methods and Results: Using cultured murine cortical neurons, herein it is demonstrated that synaptic signals generated by cultures undergoing glutamate-induced hyperactivity can invoke similar effects in other cultures not exposed to elevated glutamate. Conclusion: Since sequential synaptic connectivity can encompass extensive cortical regions, this study presents a potential additional contributor to the spread of damage resulting from glutamate excitotoxicity and should be considered in attempts to mitigate neurodegeneration.