Schizophrenia is a common debilitating disease characterized by continuous or relapsing episodes of psychosis. Although the molecular mechanisms underlying this psychiatric illness remain incompletely understood, a growing body of clinical, pharmacological, and genetic evidence suggests that G protein-coupled receptors (GPCRs) play a critical role in disease development, progression, and treatment. This pivotal role is further highlighted by the fact that GPCRs are the most common targets for antipsychotic drugs. The GPCRs activation evokes slow synaptic transmission through several downstream pathways, many of them engaging intracellular Ca²⁺ mobilization. Dysfunctions of the neurotransmitter systems involving the action of GPCRs in the frontal and limbic-related regions are likely to underly the complex picture that includes the whole spectrum of positive and negative schizophrenia symptoms. Therefore, the progress in our understanding of GPCRs function in the control of brain cognitive functions is expected to open new avenues for selective drug development. In this paper, we review and synthesize the recent data regarding the contribution of neurotransmitter-GPCRs signaling to schizophrenia symptomology.

The family of myocyte enhancer factor 2 (MEF2) transcription factors comprises four highly conserved members that play an important role in the nervous system. They appear in precisely defined time frames in the developing brain to turn on and turn off genes affecting growth, pruning and survival of neurons. MEF2s are known to dictate neuronal development, synaptic plasticity and restrict the number of synapses in the hippocampus, thus affecting learning and memory formation. In primary neurons, negative regulation of MEF2 activity by external stimuli or stress conditions is known to induce apoptosis, albeit the pro or antiapoptotic action of MEF2 depends on the neuronal maturation stage. By contrast, enhancement of MEF2 transcriptional activity protects neurons from apoptotic death both in vitro and in preclinical models of neurodegenerative diseases. A growing body of evidence places this transcription factor in the center of many neuropathologies associated with age-dependent neuronal dysfunctions or gradual but irreversible neuron loss. In this work, we discuss how the altered function of MEF2s during development and in adulthood affecting neuronal survival may be linked to neuropsychiatric disorders.

The dysregulation of intracellular calcium levels is a critical factor in neurodegeneration, leading to the aberrant activation of calcium-dependent processes and, ultimately, cell death. Ca²⁺ signals vary in magnitude, duration, and the type of neuron affected. A moderate Ca²⁺ concentration can initiate certain cellular repair pathways and promote neuroregeneration. While the peripheral nervous system exhibits an intrinsic regenerative capability, the central nervous system has limited self-repair potential. There is evidence that significant variations exist in evoked calcium responses and axonal regeneration among neurons, and individual differences in regenerative capacity are apparent even within the same type of neurons. Furthermore, some studies have shown that neuronal activity could serve as a potent regulator of this process. The spatio-temporal patterns of calcium dynamics are intricately controlled by a variety of proteins, including channels, ion pumps, enzymes, and various calcium-binding proteins, each of which can exert either positive or negative effects on neural repair, depending on the cellular context. In this concise review, we focus on several calcium-associated proteins such as CaM kinase II, GAP-43, oncomodulin, caldendrin, calneuron, and NCS-1 in order to elaborate on their roles in the intrinsic mechanisms governing neuronal regeneration following traumatic damage processes.

Vitamin C (ascorbic acid) is well known for its potent antioxidant properties, as it can neutralize ROS and free radicals, thereby protecting cellular elements from oxidative stress. It predominantly exists as an ascorbate anion and after oxidation to dehydroascorbic acid and further breakdown, is removed from the cells. In nervous tissue, a progressive decrease in vitamin C level or its prolonged deficiency have been associated with an increased risk of disturbances in neurotransmission, leading to dysregulation in brain function. Therefore, understanding the regulatory function of vitamin C in antioxidant defence and identification of its molecular targets deserves more attention. One of the key signalling ions is calcium and a transient rise in its concentration is crucial for all neuronal processes. Extracellular Ca²⁺ influx (through specific ion channels) or Ca²⁺ release from intracellular stores (endoplasmic reticulum, mitochondria) are precisely controlled. Ca²⁺ regulates the functioning of the CNS, including growth, development, myelin formation, synthesis of catecholamines, modulation of neurotransmission and antioxidant protection. A growing body of evidence indicates a unique role for vitamin C in these processes. In this short review, we focus on vitamin C in the regulation of calcium-involved pathways under physiological and stress conditions in the brain.

Ketamine is a non-competitive antagonist of NMDA (N-methyl-D-aspartate) receptor, which has been in clinical practice for over a half century. Despite recent data suggesting its harmful side effects, such as neuronal loss, synapse dysfunction or disturbed neural network formation, the drug is still applied in veterinary medicine and specialist anesthesia. Several lines of evidence indicate that structural and functional abnormalities in the nervous system caused by ketamine are crosslinked with the imbalanced activity of multiple Ca²⁺-regulated signaling pathways. Due to its ubiquitous nature, Ca²⁺ is also frequently located in the center of ketamine action, although the precise mechanisms underlying drug’s negative or therapeutic properties remain mysterious for the large part. This review seeks to delineate the relationship between ketamine-triggered imbalance in Ca²⁺ homeostasis and functional consequences for downstream processes regulating key aspects of neuronal function.

Calcium in mammalian neurons is essential for developmental processes, neurotransmitter release, apoptosis, and signal transduction. Incorrectly processed Ca²⁺ signal is well-known to trigger a cascade of events leading to altered response to variety of stimuli and persistent accumulation of pathological changes at the molecular level. To counterbalance potentially detrimental consequences of Ca²⁺, neurons are equipped with sophisticated mechanisms that function to keep its concentration in a tightly regulated range. Calcium pumps belonging to the P-type family of ATPases: plasma membrane Ca²⁺-ATPase (PMCA), sarco/endoplasmic Ca²⁺-ATPase (SERCA) and secretory pathway Ca²⁺-ATPase (SPCA) are considered efficient line of defense against abnormal Ca²⁺ rises. However, their role is not limited only to Ca²⁺ transport, as they present tissue-specific functionality and unique sensitive to the regulation by the main calcium signal decoding protein—calmodulin (CaM). Based on the available literature, in this review we analyze the contribution of these three types of Ca²⁺-ATPases to neuropathology, with a special emphasis on mental diseases.