Functional and molecular alterations in the cerebellum are among the most widely recognised associates of autism spectrum disorders (ASD). As a critical computational hub of the brain, the cerebellum controls and coordinates a range of motor, affective and cognitive processes. Despite well-described circuits and integrative mechanisms, specific changes that underlie cerebellar impairments in ASD remain elusive. Studies in experimental animals have been critical in uncovering molecular pathology and neuro-behavioural correlates, providing a model for investigating complex disease conditions. Herein, we review commonalities and differences of the most extensively characterised genetic lines of ASD with reference to the cerebellum. We revisit structural, functional, and molecular alterations which may contribute to neurobehavioral phenotypes. The cross-model analysis of this study provides an integrated outlook on the role of cerebellar alterations in pathobiology of ASD that may benefit future translational research and development of therapies.

• Klíčová slova
• Autism spectrum disorders, Cerebellum, Fmr1, Mecp2, Nlgn3/4, Purkinje neurons, Tsc1/2,
• MeSH
• modely genetické MeSH
• modely nemocí na zvířatech * MeSH
• mozeček * patofyziologie   patologie   MeSH
• poruchy autistického spektra * genetika   patologie   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Glaucoma, one of the most common causes of blindness in developing countries today, involves a progressive loss of neural cells in the optic nerve that leads to progressive, irreversible vision loss. Increased intraocular pressure (IOP) presents as a major risk factor for glaucoma, although there exist cases of glaucoma patients with normal IOP that exhibit damage to retinal ganglion cells (RGCs) and the optic nerve. However, treatment approaches have maintained their focus on modifying IOP due to a lack of other modifiable risks factors. Traditional concepts in glaucoma involve the neuronal environment and external effects as a source of causative factors; however, studies have yet to investigate whether the molecular profile of RGCs in glaucoma patients makes them more vulnerable and/or susceptible to external damage. Our hypothesis states that molecular changes at the whole cell, gene expression, and electrophysiological level of the neurons can contribute to their degeneration. Herein, we briefly describe different types of glaucoma and any similarities to different molecular and cellular features of neurodegeneration. To test our hypothesis, we describe human induced pluripotent stem cells (hiPSCs) as a reliable cellular tool to model neurodegenerative aspects of glaucoma to reveal the multiple pathological molecular mechanisms underlying disease development.

• Klíčová slova
• 3D organoids, Glaucoma, disease modelling, induced pluripotent stem cells, neurodegenerative diseases, retinal ganglion cells,
• MeSH
• genetická predispozice k nemoci * MeSH
• glaukom * etiologie   genetika   metabolismus   patologie   MeSH
• indukované pluripotentní kmenové buňky * MeSH
• lidé MeSH
• neurodegenerativní nemoci * etiologie   genetika   metabolismus   patologie   MeSH
• retinální gangliové buňky * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

Several rare or orphan diseases have been characterized that singly affect low numbers of people, but cumulatively reach ∼6%-10% of the population in Europe and in the United States. Human genetics has shown to be broadly effective when evaluating subjacent genetic defects such as orphan genetic diseases, but on the other hand, a modest progress has been achieved toward comprehending the molecular pathologies and designing new therapies. Chemical genetics, placed at the interface of chemistry and genetics, could be employed to understand the molecular mechanisms of subjacent illnesses and for the discovery of new remediation processes. This review debates current progress in chemical genetics, and how a variety of compounds and reaction mechanisms can be used to study and ultimately treat rare genetic diseases. We focus here on a study involving Amyotrophic lateral sclerosis (ALS), Duchenne Muscular Dystrophy (DMD), Spinal muscular atrophy (SMA) and Familial Amyloid Polyneuropathy (FAP), approaching different treatment methods and the reaction mechanisms of several compounds, trying to elucidate new routes capable of assisting in the treatment profile.

• Klíčová slova
• Amyotrophic lateral sclerosis, Duchenne muscular dystrophy, Neurological orphan disease, Spinal muscular atrophy and familial amyloid polyneuropathy,
• MeSH
• léčivé přípravky * MeSH
• lidé MeSH
• nemoci nervového systému * farmakoterapie   genetika   patofyziologie   MeSH
• vzácné nemoci * farmakoterapie   genetika   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• léčivé přípravky * MeSH

Amphetamine-related drugs, such as 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine (METH), are popular recreational psychostimulants. Several preclinical studies have demonstrated that, besides having the potential for abuse, amphetamine-related drugs may also elicit neurotoxic and neuroinflammatory effects. The neurotoxic potentials of MDMA and METH to dopaminergic and serotonergic neurons have been clearly demonstrated in both rodents and non-human primates. This review summarizes the species-specific cellular and molecular mechanisms involved in MDMA and METH-mediated neurotoxic and neuroinflammatory effects, along with the most important behavioral changes elicited by these substances in experimental animals and humans. Emphasis is placed on the neuropsychological and neurological consequences associated with the neuronal damage. Moreover, we point out the gap in our knowledge and the need for developing appropriate therapeutic strategies to manage the neurological problems associated with amphetamine-related drug abuse.

• Klíčová slova
• 3,4-Methylenedioxymethamphetamine, Dopamine, Ecstasy, MDMA, METH, Methamphetamine, Mouse, Neurodegeneration, Neuroinflammation neurotoxicity, Non-human primate, Rat,
• MeSH
• lidé MeSH
• methamfetamin škodlivé účinky   MeSH
• mozek účinky léků   MeSH
• N-methyl-3,4-methylendioxyamfetamin škodlivé účinky   MeSH
• neurotoxické syndromy patologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• methamfetamin MeSH
• N-methyl-3,4-methylendioxyamfetamin MeSH

Copper is an important trace element that is required for essential enzymes. However, due to its redox activity, copper can also lead to the generation of toxic reactive oxygen species. Therefore, cellular uptake, storage as well as export of copper have to be tightly regulated in order to guarantee sufficient copper supply for the synthesis of copper-containing enzymes but also to prevent copper-induced oxidative stress. In brain, copper is of importance for normal development. In addition, both copper deficiency as well as excess of copper can seriously affect brain functions. Therefore, this organ possesses ample mechanisms to regulate its copper metabolism. In brain, astrocytes are considered as important regulators of copper homeostasis. Impairments of homeostatic mechanisms in brain copper metabolism have been associated with neurodegeneration in human disorders such as Menkes disease, Wilson's disease and Alzheimer's disease. This review article will summarize the biological functions of copper in the brain and will describe the current knowledge on the mechanisms involved in copper transport, storage and export of brain cells. The role of copper in diseases that have been connected with disturbances in brain copper homeostasis will also be discussed.

• Klíčová slova
• Astrocytes, Brain, Copper, Neurodegeneration, Transport,
• MeSH
• astrocyty fyziologie   MeSH
• homeostáza MeSH
• lidé MeSH
• měď metabolismus   MeSH
• mozek fyziologie   patofyziologie   MeSH
• neurodegenerativní nemoci patofyziologie   MeSH
• neurony fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• měď MeSH

Firstly, the noetic value of the ontogenetic approach to the problems of learning and memory is emphasized; then the heterochrony and uneven time course of the development of neural systems are accentuated, which fully holds for the basic cognitive functions. Contrary to a broadly accepted opinion, that inhibitory learning develops later in the ontogeny, using a special method of passive avoidance (with gentle air flow inciting the new-born animal to move), the ability of new-born rats to learn an inhibitory reaction even several hours after delivery and remember it for 24 hr has been proven; special control experiments have excluded any possibility that it is a non-specific reaction. To get it, the specific features of the neonatal organism are to be considered and its functional capabilities not to be overlooked. This conditioned reaction as well as its 24 hr memory develops with a temporary reversal during several postnatal days, needing decreasing numbers of trials to meet the criteria. In the analysis of their mechanisms, it has been shown that adequate functioning of peripheral receptor zones providing afferent inputs from somatosensory areas of the conditioned stimulus is considerably involved in their establishment. Increased dendritic branching has been found in hippocampus and Meynert nucleus the following day after learning in the neonatal period. Special attention is devoted to the involvement of transmitters and/or modulators; the action of acetylcholine, noradrenaline, dopamine and nitric oxide has been discovered during the first postnatal hours; their application after meeting criteria displays a time and age dependent effect with a general characteristic of memory improvement. Neonatal learning under nitric oxide influence changes nitric oxide-synthase content in the brain. Increasing dopamine and nitric oxide availability in the brain improves both learning and memory, and their joint application positively alleviates these phenomena further. Dopamine and its D1 receptor agonists counterbalance decreased nitric oxide after nitric oxide synthase blockade; increased nitric oxide in brain and dopamine receptor antagonists similarly counterbalance each other.

• MeSH
• krysa rodu Rattus psychologie   MeSH
• novorozená zvířata psychologie   MeSH
• paměť fyziologie   MeSH
• učení fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus psychologie   MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH