Polymer biomaterials are being considered for tissue regeneration due to the possibility of resembling different extracellular matrix characteristics. However, most current scaffolds cannot respond to physical-chemical modifications of the cell microenvironment. Stimuli-responsive materials, such as electroactive smart polymers, are increasingly gaining attention once they can produce electrical potentials without external power supplies. The presence of piezoelectricity in human tissues like cartilage and bone highlights the importance of electrical stimulation in physiological conditions. Although poly(vinylidene fluoride) (PVDF) is one of the piezoelectric polymers with the highest piezoelectric response, it is not biodegradable. Poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) is a promising copolymer of poly(hydroxybutyrate) (PHB) for tissue engineering and regeneration applications. It offers biodegradability, piezoelectric properties, biocompatibility, and bioactivity, making it a superior option to PVDF for biomedical purposes requiring biodegradability. Magnetoelectric polymer composites can be made by combining magnetostrictive particles and piezoelectric polymers to further tune their properties for tissue regeneration. These composites convert magnetic stimuli into electrical stimuli, generating local electrical potentials for various applications. Cobalt ferrites (CFO) and piezoelectric polymers have been combined and processed into different morphologies, maintaining biocompatibility for tissue engineering. The present work studied how PHBV/CFO microspheres affected neural and glial response in spinal cord cultures. It is expected that the electrical signals generated by these microspheres due to their magnetoelectric nature could aid in tissue regeneration and repair. PHBV/CFO microspheres were not cytotoxic and were able to impact neurite outgrowth and promote neuronal differentiation. Furthermore, PHBV/CFO microspheres led to microglia activation and induced the release of several bioactive molecules. Importantly, magnetically stimulated microspheres ameliorated cell viability after an in vitro ROS-induced lesion of spinal cord cultures, which suggests a beneficial effect on tissue regeneration and repair.

The transcription factor activating protein two gamma (AP2γ) is an important regulator of neurogenesis both during embryonic development as well as in the postnatal brain, but its role for neurophysiology and behavior at distinct postnatal periods is still unclear. In this work, we explored the neurogenic, behavioral, and functional impact of a constitutive and heterozygous AP2γ deletion in mice from early postnatal development until adulthood. AP2γ deficiency promotes downregulation of hippocampal glutamatergic neurogenesis, altering the ontogeny of emotional and memory behaviors associated with hippocampus formation. The impairments induced by AP2γ constitutive deletion since early development leads to an anxious-like phenotype and memory impairments as early as the juvenile phase. These behavioral impairments either persist from the juvenile phase to adulthood or emerge in adult mice with deficits in behavioral flexibility and object location recognition. Collectively, we observed a progressive and cumulative impact of constitutive AP2γ deficiency on the hippocampal glutamatergic neurogenic process, as well as alterations on limbic-cortical connectivity, together with functional behavioral impairments. The results herein presented demonstrate the modulatory role exerted by the AP2γ transcription factor and the relevance of hippocampal neurogenesis in the development of emotional states and memory processes.

"Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is the third most prevalent recessive ataxia, characterized by childhood onset of progressive cerebellar ataxia, spasticity, motor sensory neuropathy, axonal demyelination, and Purkinje cell loss. ARSACS is caused by loss-of- function mutations in the SACS gene, which encodes sacsin, a 520 kDa multimodular protein with a partially understood function. Several lines of evidence suggest that sacsin is involved in chaperone activities, promotes the proper polymerization of the neuronal intermediate filaments (i.e., neurofilaments and vimentin), is linked to mitochondrial dynamics, and bioenergetics and regulates organelle positioning by regulating cytoskeletal dynamics.(...)"

Astrocytes are key players in the regulation of brain development and function. They sense and respond to the surrounding activity by elevating their intracellular calcium (Ca²⁺) levels. These astrocytic Ca²⁺ elevations emerge from different sources and display complex spatio-temporal properties. Ca²⁺ elevations are spatially distributed in global (soma and main processes) and/or focal regions (microdomains). The inositol 1,4,5-trisphosphate receptor type 2 knockout (IP<inf>3</inf>R2 KO) mouse model lacks global Ca²⁺ elevations in astrocytes, and it has been used by different laboratories. However, the constitutive deletion of IP<inf>3</inf>R2 during development may trigger compensating phenotypes, which could bias the results of experiments using developing or adult mice. To address this issue, we performed a detailed neurodevelopmental evaluation of male and female IP<inf>3</inf>R2 KO mice, during the first 21 days of life, as well as an evaluation of motor function, strength and neurological reflexes in adult mice. Our results show that male and female IP<inf>3</inf>R2 KO mice display a normal acquisition of developmental milestones, as compared with wild-type (WT) mice. We also show that IP<inf>3</inf>R2 KO mice display normal motor coordination, strength and neurological reflexes in adulthood. To exclude a potential compensatory overexpression of other IP<inf>3</inf>Rs, we quantified the relative mRNA levels of all 3 subtypes, in brain tissue. We found that, along with the complete deletion of Itpr2, there is no compensatory expression of Itpr1 or Itrp3. Overall, our results show that the IP<inf>3</inf>R2 KO mouse is a reliable model to study the functional impact of global IP<inf>3</inf>R2-dependent astrocytic Ca²⁺ elevations.