IGF1 gene therapy in middle-aged female rats delays reproductive senescence through its effects on hypothalamic GnRH and kisspeptin neurons.

The process of aging is the result of progressive loss of homeostasis and functional body impairment, including the central nervous system, where the hypothalamus plays a key role in regulating aging mechanisms. The consequences of aging include a chronic proinflammatory environment in the hypothalamus that leads to decreased secretion of gonadotropin-releasing hormone (GnRH) and impairs kisspeptin neuron functionality. In this work, we investigated the effect of insulin-like growth factor 1 (IGF1) gene therapy on hypothalamic kisspeptin/GnRH neurons and on microglial cells, that mediate the inflammatory process related with the aging process.

IGF-1 Gene Transfer Modifies Inflammatory Environment and Gene Expression in the Caudate-Putamen of Aged Female Rat Brain.

Brain aging is characterized by chronic neuroinflammation caused by activation of glial cells, mainly microglia, leading to alterations in homeostasis of the central nervous system. Microglial cells are constantly surveying their environment to detect and respond to diverse signals. During aging, microglia undergoes a process of senescence, characterized by loss of ramifications, spheroid formation, and fragmented processes, among other abnormalities.

IGF1 Gene Therapy Reversed Cognitive Deficits and Restored Hippocampal Alterations After Chronic Spinal Cord Injury.

The hippocampus is implicated in the generation of memory and learning, processes which involve extensive neuroplasticity. The generation of hippocampal adult-born neurons is particularly regulated by glial cells of the neurogenic niche and the surrounding microenvironment. Interestingly, recent evidence has shown that spinal cord injury (SCI) in rodents leads to hippocampal neuroinflammation, neurogenesis reduction, and cognitive impairments.

Intracisternal IGF-1 gene therapy abrogates kainic acid-induced excitotoxic damage of the rat spinal cord.

Development of alternative therapies for treating functional deficits after different neurological damages is a challenge in neuroscience. Insulin-like growth factor-1 (IGF-1) is a potent neurotrophic factor exerting neuroprotective actions in brain and spinal cord. It is used to prevent or treat injuries of the central nervous system using different administration routes in different animal models.

Sex frailty differences in ageing mice: Neuropathologies and therapeutic projections.

It is well-established that females live longer than males. Paradoxically, women tend to have poorer health, a condition often named sex frailty. The aim of this study was to evaluate possible frailty predictors in older mice in a sex-specific manner, in order to employ these predictors to follow-up therapy efficiency.

Novel adenoviral IGF-1 administration modulates the association between depressive symptoms and aging: Does gender matter?

Depression is an illness of multifactorial origin and it seems to involve the dysregulation of many physiological processes. It also has been associated with age and a decreased in the expression of some neurotrophins. However, there are not unique animal models to assay depressive-like behavior, with male and females responding differently.

Intracerebroventricular streptozotocin induces impaired Barnes maze spatial memory and reduces astrocyte branching in the CA1 and CA3 hippocampal regions.

Sporadic Alzheimer's disease (SAD) is the most common form of dementia; therefore, there is an urgent need for a model that recapitulates the main pathologic hallmarks of this disease. The intracerebroventricular (icv) injection of streptozotocin (icv-STZ) in rats constitutes a promising model, and thus, icv-STZ rats develop insulin-resistant brain state and cognitive impairments. Even though a great piece of studies has hitherto described this system as a model for SAD, further behavioral and morphometric studies are still needed to fully characterize it.

Magnetofection Enhances Adenoviral Vector-based Gene Delivery in Skeletal Muscle Cells.

The goal of magnetic field-assisted gene transfer is to enhance internalization of exogenous nucleic acids by association with magnetic nanoparticles (MNPs). This technique named magnetofection is particularly useful in difficult-to-transfect cells. It is well known that human, mouse, and rat skeletal muscle cells suffer a maturation-dependent loss of susceptibility to Recombinant Adenoviral vector (RAd) uptake.