Astrocytes, the most numerous cells in the brain, weave the canvas of the grey matter and act as the main element of the homoeostatic system of the brain. They shape the microarchitecture of the brain, form neuronal-glial-vascular units, regulate the blood–brain barrier, control microenvirionment of the central nervous system and defend nervous system against multitude of insults. Here, we overview the pathological potential of astroglia in various forms of dementias, and hypothesise that both atrophy of astroglia and reactive hypertrophic astrogliosis may develop in parallel during neurodegenerative processes resulting in dementia. We also show that in the transgenic model of Alzheimer's disease, reactive hypertrophic astrocytes surround the neuritic plaques, whereas throughout the brain parenchyma astroglial cells undergo atrophy. Astroglial atrophy may account for early changes in synaptic plasticity and cognitive impairments, which develop before gross neurodegenerative alterations.

SUMMARY: Is oxytocin the hormone of happiness? Probably not. However, this small nine amino acid peptide is involved in a wide variety of physiological and pathological functions such as sexual activity, penile erection, ejaculation, pregnancy, uterus contraction, milk ejection, maternal behavior, osteoporosis, diabetes, cancer, social bonding, and stress, which makes oxytocin and its receptor potential candidates as targets for drug therapy. In this review, we address the issues of drug design and specificity and focus our discussion on recent findings on oxytocin and its heterotrimeric G protein‐coupled receptor OTR. In this regard, we will highlight the following topics: (i) the role of oxytocin in behavior and affectivity, (ii) the relationship between oxytocin and stress with emphasis on the hypothalamo–pituitary–adrenal axis, (iii) the involvement of oxytocin in pain regulation and nociception, (iv) the specific action mechanisms of oxytocin on intracellular Ca²⁺ in the hypothalamo neurohypophysial system (HNS) cell bodies, (v) newly generated transgenic rats tagged by a visible fluorescent protein to study the physiology of vasopressin and oxytocin, and (vi) the action of the neurohypophysial hormone outside the central nervous system, including the myometrium, heart and peripheral nervous system. As a short nine amino acid peptide, closely related to its partner peptide vasopressin, oxytocin appears to be ideal for the design of agonists and antagonists of its receptor. In addition, not only the hormone itself and its binding to OTR, but also its synthesis, storage and release can be endogenously and exogenously regulated to counteract pathophysiological states. Understanding the fundamental physiopharmacology of the effects of oxytocin is an important and necessary approach for developing a potential pharmacotherapy.

Extracellular space (ECS) volume fraction (α), ECS tortuosity (λ), and nonspecific uptake ( k‘), three parameters affecting the diffusion of substances in nervous tissue, were studied during ischemia and anoxia in the rat spinal cord gray matter in vivo. Progressive ischemia evoked by exsanguination, as well as anoxia evoked by respiratory or cardiac arrest, produced prominent extracellular K⁺ and pH changes closely related to a decrease in blood pressure and amplitude of field potentials. With use of ion-selective microelectrodes, the changes in the diffusion parameters were measured by quantitative analysis of concentration-time profiles of tetramethylammonium (TMA⁺) applied by iontophoresis concomitantly with ionic shifts. Under normoxic conditions (in rats with blood pressure of 80–110 mm Hg) diffusion parameters in the dorsal horn gray matter at depth 500–900 μm were as follows: α = 0.20 ± 0.019, λ = 1.62 ± 0.12, k’ = 4.6 ± 2.5 × 10⁻³ s⁻¹ (mean ± SD, n = 39). Extracellular K⁺, pH, and diffusion properties gradually changed during progressive ischemia. As the blood pressure fell to 50–60 mm Hg and field potential amplitude to 20–60%, K⁺ rose to 6–12 m M, pH_e fell by ∼0.05–0.1 pH unit, and volume fraction of the ECS significantly decreased, to α = 0.16 ± 0.019 (n = 22). Even though the tortuosity remained virtually constant, the nonspecific uptake significantly decreased to k‘ = 3.4 ± 1.8 × 10⁻³ s⁻¹. As the blood pressure fell to 20–30 mm Hg and field potential amplitude to 0–6%, K⁺ rose to 60–70 m M, pH_e fell by ∼0.6–0.8 pH unit, and all three diffusion parameters significantly changed. The ECS volume fraction decreased to α = 0.05 ± 0.021, tortuosity increased to λ = 2.00 ± 0.24, and TMA⁺ uptake decreased to k’ = 1.5 ± 1.6 × 10⁻³ s⁻¹ (n = 12). No further increase in extracellular K⁺ or changes in the α were found during and up to 120 min after the death of the animal. However, there was a further significant increase in λ = 2.20 ± 0.14 and decrease in k‘ = 0.4 ± 0.3 × 10⁻³ s⁻¹ (n = 24). The acid shift reached its maximum level at ∼5–10 min after respiratory arrest and then the pH_e gradually increased by ∼0.2 unit. Full recovery to “normoxic” diffusion parameters was achieved after reinjection of the blood or after an injection of noradrenaline during severe ischemia, if this resulted in a rise in blood pressure above 80 mm Hg and a decrease in extracellular K⁺ below 12 m M. At ∼10 and 30 min after this recovery, the ECS volume fraction significantly increased above “normoxic” values, to α = 0.25 ± 0.016 (n = 7) and α = 0.30 ± 0.021 (n = 6), respectively. The λ and k’ were not significantly different from the values found under normoxic conditions. Our data represent the first detailed in vivo measurements of diffusion parameters α, λ, and k‘ during and after progressive ischemia and anoxia. The observed substantial changes in the diffusion parameters could affect the diffusion and aggravate the accumulation of ions, neurotransmitters, metabolic substances, and drugs used in therapy of nervous diseases and thus contribute to ischemic CNS damage.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by the loss of cognitive functions, reflecting pathological damage to the medial prefrontal cortex (mPFC) as well as to the hippocampus and the entorhinal cortex. Astrocytes maintain the internal homeostasis of the CNS and are fundamentally involved in neuropathological processes, including AD. Here, we analysed the astrocytic cytoskeletal changes within the mPFC of a triple transgenic mouse model of AD (3 × Tg‐AD) by measuring the surface area and volume of glial fibrillary acidic protein (GFAP)‐positive profiles in relation to the build‐up and presence of amyloid‐β (Aβ), and compared the results with those found in non‐transgenic control animals at different ages. 3 × Tg‐AD animals showed clear astroglial cytoskeletal atrophy, which appeared at an early age (3 months; 33% and 47% decrease in GFAP‐positive surface area and volume, respectively) and remained throughout the disease progression at 9, 12 and 18 months old (29% and 36%; 37% and 35%; 43% and 37%, respectively). This atrophy was independent of Aβ accumulation, as only a few GFAP‐positive cells were localized around Aβ aggregates, which suggests no direct relationship with Aβ toxicity. Thus, our results indicate that the progressive reduction in astrocytic branching and domain in the mPFC can account for the integrative dysfunction leading to the cognitive deficits and memory disturbances observed in AD.

Astrocytes control tissue equilibrium and hence define the homoeostasis and function of the CNS (central nervous system). Being principal homoeostatic cells, as...