Neuroplasticity is the capacity of neural networks in the brain to alter through development and rearrangement. It can be classified as structural and functional plasticity. The hippocampus is more susceptible to neuroplasticity as compared to other brain regions. Structural modifications in the hippocampus underpin several neurodegenerative diseases that exhibit cognitive and emotional dysregulation. This article reviews the findings of several preclinical and clinical studies about the role of structural plasticity in the hippocampus in neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and multiple sclerosis. In this study, literature was surveyed using Google Scholar, PubMed, Web of Science, and Scopus, to review the mechanisms that underlie the alterations in the structural plasticity of the hippocampus in neurodegenerative diseases. This review summarizes the role of structural plasticity in the hippocampus for the etiopathogenesis of neurodegenerative diseases and identifies the current focus and gaps in knowledge about hippocampal dysfunctions. Ultimately, this information will be useful to propel future mechanistic and therapeutic research in neurodegenerative diseases.

This study aimed to investigate whether the Protaetia brevitarsis seulensis (PB)’ water extract (PBWE) ameliorates trimethyltin (TMT)-induced seizures and hippocampal neurodegeneration. To investigate the potential neuroprotective effect of the PBWE in vitro, a lactate dehydrogenase (LDH) assay was conducted in TMT-treated primary cultures of mouse hippocampal neurons. In TMT-treated adult C57BL/6 mice, behavioral and histopathological changes were evaluated by seizure scoring and Fluoro-Jade C staining, respectively. In our in vitro assay, we observed that pretreating mice hippocampal neuron cultures with the PBWE reduced TMT-induced cytotoxicity, as indicated by the decreased LDH release. Furthermore, pretreatment with the PBWE alleviated seizures and hippocampal neurodegeneration in TMT-treated mice. The antioxidant activity of the PBWE increased in a dose-dependent manner; moreover, pretreatment with the PBWE mitigated the TMT-induced Nrf2 stimulation. In addition, six major compounds, including adenine, hypoxanthine, uridine, adenosine, inosine, and benzoic acid, were isolated from the PBWE, and among them, inosine and benzoic acid have been confirmed to have an essential antioxidative activity. In conclusion, the PBWE ameliorated TMT-induced toxicity in hippocampal neurons in both in vitro and in vivo assays, through a potential antioxidative effect. Our findings suggest that the PBWE may have pharmacotherapeutic potential in neurodegenerative diseases such as seizures or epilepsy.

High-dose salicylate induces temporary moderate hearing loss and the perception of a high-pitched tinnitus in humans and animals. Previous studies demonstrated that high doses of salicylate increase N-methyl-d-aspartate (NMDA) receptor levels, resulting in a rise in Ca²⁺ influx and induction of excitotoxicity. Glutamate excitotoxicity is associated with failure in the maintenance of calcium homeostasis, mitochondrial dysfunction, and production of reactive oxygen species (ROS). Valproic acid (VPA) is widely used for the management of bipolar disorder, epilepsy, and migraine headaches, and is known to regulate NMDA receptor activity. In this study, we examined the beneficial effects of VPA in a salicylate-induced tinnitus model in vitro and in vivo. Cells were pretreated with VPA followed by salicylate treatment. The expression levels of NMDA receptor subunit NR2B, phosphorylated cAMP response element-binding protein—an apoptosis marker, and intracellular levels of ROS were measured using several biochemical techniques. We observed increased expression of NR2B and its related genes TNFα and ARC, increased intracellular ROS levels, and induced expression of cleaved caspase-3. These salicylate-induced changes were attenuated in the neuronal cell line SH-SY5Y and rat cortical neurons after VPA pretreatment. Together, these results provide evidence of the beneficial effects of VPA in a salicylate-induced temporary hearing loss and tinnitus model.

Purpose: Parkinson disease (PD) is a progressive neurodegenerative disorder in which dopaminergic (DAergic) systems are destroyed (particularly in the nigrostriatal system), causing both motor and nonmotor symptoms. Hippocampal neuroplasticity is altered in PD animal models, resulting in nonmotor dysfunctions. However, little is known about the precise mechanism underlying the hippocampal dysfunctions in PD.Methods: Striatal 6-hydroxydopamine (6-OHDA) infusions were performed unilaterally in adult Sprague Dawley rats. Both motor and nonmotor symptoms alongside the expression of tyrosine hydroxylase (TH) in the substantia nigra and striatum were confirmed in 6-OHDA-lesioned rats. The neuronal architecture in the hippocampus was analyzed by Golgi staining.Results: During the 7–8 weeks after infusion, the 6-OHDA-lesioned rats exhibited motor and nonmotor dysfunctions (especially anxiety/depression-like behaviors). Rats with unilateral 6-OHDA infusion displayed reduced TH+ immunoreactivity in the ipsilateral nigrostriatal pathway of the brain. Golgi staining revealed that striatal 6-OHDA infusion significantly decreased the dendritic complexity (i.e., number of crossing dendrites, total dendritic length, and branch points) in the ipsilateral hippocampal conus ammonis 1 (CA1) apical/basal and dentate gyrus (DG) subregions. Additionally, the dendritic spine density and morphology were significantly altered in the CA1 apical/basal and DG subregions following striatal 6-OHDA infusion. However, alteration of microglial and astrocytic distributions did not occur in the hippocampus following striatal 6-OHDA infusion.Conclusions: The present study provides anatomical evidence that the structural plasticity in the hippocampus is altered in the late phase following striatal 6-OHDA infusion in rats, possibly as a result of the prolonged suppression of the DAergic system, and independent of neuroinflammation.

(1) Objective: In order to evaluate the effect of a pre-induced mesenchymal stem cell (MSC)-coated cellulose/collagen nanofibrous nerve conduit on facial nerve regeneration in a rat model both in vitro and in vivo. (2) Methods: After fabrication of the cellulose/collagen nanofibrous conduit, its lumen was coated with either MSCs or pre-induced MSCs. The nerve conduit was then applied to the defective main trunk of the facial nerve. Rats were randomly divided into three treatment groups (n = 10 in each): cellulose/collagen nanofiber (control group), cellulose/collagen nanofiber/MSCs (group I), and cellulose/collagen nanofiber/pre-induced MSCs (group II). (3) Results Fibrillation of the vibrissae of each group was observed, and action potential threshold was compared 8 weeks post-surgery. Histopathological changes were also observed. Groups I and II showed better recovery of vibrissa fibrillation than the control group. (4) Conclusions: Group II, treated with the pre-induced MSC-coated cellulose/collagen nanofibrous nerve conduit, showed the highest degree of recovery based on functional and histological evaluations.