Preface

As a member of the neurotrophin family of proteins, brain-derived neurotrophic factor (BDNF) plays a vital role in maintaining optimal brain function, encompassing functions such as synaptic plasticity, cellular differentiation, learning processes, and the preservation of nerve cells. Neural plasticity, the nervous system's capability to adapt to varying environmental conditions, involves a diverse array of structural and functional mechanisms. Due to its robust neuroprotective properties and recently uncovered antiinflammatory and anti-apoptotic attributes observed both in laboratory settings and in living organisms, BDNF has long been suggested as a potential preventative measure against neurodegeneration.

BDNF has emerged as a significant player in the pathophysiology of numerous psychiatric disorders, including depression, anxiety, schizophrenia, and bipolar disorder. Empirical evidence has consistently indicated that individuals afflicted with these conditions frequently exhibit lower BDNF levels in both their blood and brains.

The precise role of BDNF in psychiatric disorders remains an active area of research. However, scientists hypothesize that BDNF may contribute to several fundamental symptoms observed in these disorders, such as mood fluctuations, cognitive impairments, and social withdrawal. In addition to these considerations, BDNF has some potential additional benefits in addressing psychiatric disorders. *Enhancing mood*: BDNF can stimulate the release of mood-regulating neurotransmitters, such as serotonin and dopamine. *Reducing anxiety and stress*: BDNF has the capacity to modulate the stress response, contributing to a reduction in anxiety symptoms. *Enhancing cognitive function*: BDNF may enhance memory, attention, and executive function, functions that can be compromised in individuals with psychiatric disorders. *Facilitating social interaction*: BDNF can bolster the development and operation of brain circuits associated with social interaction.

BDNF has emerged as a significant factor in the understanding of autism spectrum disorder (ASD) pathophysiology. Studies have consistently indicated that individuals with ASD often exhibit lower levels of BDNF in both their blood and brains. Moreover, there is evidence of BDNF gene variants being linked to an increased risk of ASD.

The precise role of BDNF in ASD remains a subject of ongoing research. Nonetheless, scientists posit that BDNF may contribute to some of the central symptoms associated with ASD, including challenges in social communication and the presence of narrow interests.

BDNF stands as a promising target for therapeutic interventions in ASD. Current efforts by researchers are focused on the development of novel drugs and therapies designed to elevate BDNF levels or enhance BDNF signaling. It is crucial to pinpoint the specific BDNF pathways that play a role in ASD and create biomarkers capable of predicting treatment responses.

Beyond these considerations, BDNF has additional benefits for individuals with ASD. *Enhancing social communication skills*: BDNF can support the development and functioning of brain circuits crucial for social communication. *Mitigating restricted interests and* 

*repetitive behaviors*: BDNF may assist in diversifying interests and behaviors. *Improving cognitive function*: BDNF has the potential to enhance memory, attention, and executive function. *Alleviating anxiety and depression*: BDNF exhibits mood-boosting effects and may help reduce symptoms of anxiety and depression. BDNF represents a promising focal point for therapeutic endeavors in the context of ASD.

Ketamine is a dissociative anesthetic renowned for its rapid and enduring antidepressant effects. Researchers are also exploring its potential as a treatment for a range of psychiatric and neurological conditions, including anxiety, bipolar disorder, post-traumatic stress disorder (PTSD), and chronic pain. The therapeutic impact of ketamine is believed to be orchestrated through various mechanisms, including its influence on the N-methyl-D-aspartate receptor, modulation of glutamate signaling, and the promotion of BDNF production.

BDNF is believed to be instrumental in the formation of new synapses, vital for learning and memory. This might elucidate why ketamine displays efficacy in treating depression, a condition often accompanied by a reduction in synaptic connections. Furthermore, BDNF is thought to participate in neurogenesis, the process of generating new neurons. Neurogenesis is compromised in several psychiatric disorders, including depression, anxiety, and PTSD. Ketamine has demonstrated the potential to stimulate neurogenesis in animal models of these disorders, hinting at its potential utility in human treatments.

Collectively, evidence points to BDNF as a crucial mediator of ketamine's therapeutic effects. Ketamine-induced elevations in BDNF levels may underlie many of its therapeutic benefits, encompassing its antidepressant, anxiolytic, and analgesic properties.

The significance of BDNF extends to the realm of spinal cord injury (SCI), where it is intricately involved in the pathophysiological processes. BDNF exhibits a diverse range of neuromodulatory effects within the spinal cord. *Enhancing synaptic plasticity*: BDNF actively fosters the formation and maintenance of synapses, crucial for the preservation of learning and memory functions. *Promoting axonal regeneration*: BDNF acts as a stimulant for axonal growth, a vital process in the repair of nervous system damage. *Safeguarding neurons from demise*: BDNF provides vital support for neuronal survival and shields them from potential injury.

In preclinical models of SCI, the administration of BDNF has consistently demonstrated improvements in locomotor function, sensory perception, as well as bladder and bowel function. Moreover, BDNF has showcased its capacity to encourage axonal regeneration and protect neurons from degeneration.

Sepsis is a life-threatening condition that arises when the body's response to an infection inadvertently damages its own tissues and organs, often resulting in organ dysfunction and mortality. It stands as a leading cause of death among critically ill patients.

BDNF is a pivotal protein involved in the development and maintenance of the nervous system, with additional roles in immune system regulation. In sepsis, BDNF levels in both the blood and brain frequently experience a decline. This reduction is associated with several adverse consequences, including organ dysfunction, cognitive impairment, and fatal outcomes.

BDNF holds substantial promise as a therapeutic target for sepsis. Ongoing research endeavors are focused on the development of novel drugs and therapies designed to elevate BDNF levels or enhance BDNF signaling.

In addition to these considerations, BDNF confers additional benefits in addressing sepsis. *Mitigating inflammation*: BDNF's anti-inflammatory properties could potentially help alleviate the organ damage characteristic of sepsis. *Shielding neurons from demise*: BDNF has demonstrated the ability to safeguard neurons from the harm associated with sepsisinduced encephalopathy. *Enhancing cognitive function*: BDNF may aid in the improvement of cognitive function, a facet often impaired in survivors of sepsis. *Facilitating immune recovery*: BDNF may contribute to the restoration of immune system functionality, which is frequently dysregulated in sepsis.

Both exercise and vitamin D have demonstrated the ability to elevate BDNF levels within the brain. Exercise is believed to achieve this by boosting the production of insulin-like growth factor 1, a hormone known to stimulate BDNF production. On the other hand, vitamin D is thought to enhance BDNF levels by binding to the vitamin D receptor in the brain and activating genes associated with BDNF production.

Emerging evidence suggests that the combination of exercise and vitamin D may exert a synergistic influence on BDNF levels.

The combined impact of exercise and vitamin D on BDNF levels holds the potential for numerous advantages in maintaining brain health. Additionally, BDNF plays a vital role in shielding neurons from damage, potentially reducing the risk of developing neurodegenerative conditions such as Alzheimer's disease and Parkinson's disease. The current evidence points to the combination of exercise and vitamin D as a promising strategy for heightening BDNF levels and enhancing brain health.

This book is a comprehensive source of knowledge on BDNF and its neuroprotective functions. The chapters within offer insights into recent advancements, molecular principles, and innovative therapeutic strategies targeting neurodegenerative disorders and brain health.

> **Oytun Erbaş** ERBAS Institute of Experimental Medicine, Gebze-Kocaeli, Türkiye

> ERBAS Institute of Experimental Medicine, Illinois, USA

> **İlknur Altuntaş** ERBAS Institute of Experimental Medicine, Gebze-Kocaeli, Türkiye

Section 1
