TAT-PEP Alleviated Cognitive Impairment by Alleviating Neuronal Mitochondria Damage and Apoptosis After Cerebral...

Area of Science:

• Neuroscience
• Molecular Biology
• Biochemistry

Background:

• Paired immunoglobulin-like receptor B (PirB) is a myelin-associated inhibitory protein (MAIP) receptor crucial for axonal regeneration, synaptic plasticity, and neuronal survival post-stroke.
• A previously developed transactivator of transcription-PirB extracellular peptide (TAT-PEP) blocks MAI-PirB interactions, improving axonal regeneration and neurobehavioral recovery after stroke.
• Further investigation is needed to determine TAT-PEP's effects on cognitive function and neuronal survival.

Purpose of the Study:

• To investigate if pirb RNAi can mitigate neuronal injury by inhibiting PirB expression following oxygen-glucose deprivation (OGD) in vitro.
• To evaluate the neuroprotective effects of TAT-PEP on brain infarct volume, neurobehavioral, and cognitive function recovery.
• To elucidate the mechanisms underlying TAT-PEP's neuroprotection, including its impact on neuronal degeneration, apoptosis, oxidative stress, and mitochondrial function after ischemia-reperfusion injury.

Main Methods:

• In vitro experiments using oxygen-glucose deprivation (OGD) to induce neuronal injury and assess the effects of pirb RNAi and TAT-PEP.
• In vivo studies involving ischemia-reperfusion injury models to evaluate TAT-PEP's impact on brain infarct volume and neurobehavioral outcomes.
• Biochemical assays to measure lactate dehydrogenase (LDH) release, malondialdehyde (MDA) levels, superoxide dismutase (SOD) activity, and reactive oxygen species (ROS) accumulation.
• Analysis of mitochondrial function and the expression of apoptosis-related proteins (cleaved caspase 3, Bax, Bcl-2).

Main Results:

• TAT-PEP treatment attenuated brain infarct volume and promoted recovery of neurobehavioral and cognitive functions.
• TAT-PEP demonstrated neuroprotection by reducing neuronal degeneration and apoptosis following ischemia-reperfusion injury.
• In vitro, TAT-PEP enhanced neuron survival, decreased LDH release, reduced MDA levels, increased SOD activity, and mitigated ROS accumulation in OGD-injured neurons.
• TAT-PEP was found to protect against neuronal mitochondrial damage and modulate the expression of key apoptosis-related proteins.

Conclusions:

• PirB overexpression in neurons post-ischemic-reperfusion injury contributes to mitochondrial damage, oxidative stress, and apoptosis.
• TAT-PEP exhibits significant neuroprotective potential against ischemic stroke.
• TAT-PEP may serve as a therapeutic agent for stroke by reducing neuronal oxidative stress, mitochondrial damage, degeneration, and apoptosis.