Protocol for ovariectomy and estradiol replacement in mice.

Ovariectomy, involving the surgical removal of ovaries, and estradiol replacement facilitate the understanding of sexual dimorphism-related physiological changes, encompassing reproductive biology, metabolism, and hormone-related diseases. In this study, we present a protocol for conducting ovariectomy and estradiol replacement in mice. We describe steps for performing sham and ovariectomy operations, outline preoperative preparations, and provide details on postoperative care, including analgesia administration and the removal of surgical clips.

Astrocytic insulin receptor controls circadian behavior via dopamine signaling in a sexually dimorphic manner.

Mammalian circadian clocks respond to feeding and light cues, adjusting internal rhythms with day/night cycles. Astrocytes serve as circadian timekeepers, driving daily physiological rhythms; however, it's unknown how they ensure precise cycle-to-cycle rhythmicity. This is critical for understanding why mistimed or erratic feeding, as in shift work, disrupts circadian physiology- a condition linked to type 2 diabetes and obesity.

Hypothalamic free fatty acid receptor-1 regulates whole-body energy balance.

Objective: Free fatty acid receptor-1 (FFAR1) is a medium- and long-chain fatty acid sensing G protein-coupled receptor that is highly expressed in the hypothalamus. Here, we investigated the central role of FFAR1 on energy balance.

Methods: Central FFAR1 agonism and virogenic knockdown were performed in mice.

Hypothalamic astrocytic-BMAL1 regulates energy homeostasis in a sex-dependent manner.

Here, we demonstrate that hypothalamic astrocytic BMAL1 computes cyclic metabolic information to optimize energetic resources in a sexually dimorphic manner. Knockdown of BMAL1 in female astrocytes leads to negative energy balance and alters basal metabolic cycles without affecting circadian locomotor activity. Thus, astrocytic BMAL1 contributes to the control of energy balance through the modulation of the metabolic rate, hepatic and white adipose tissue lipogenesis, and the activity of brown adipose tissue.

Estradiol and leptin: no engagement without CITED1.

Ovarian estradiol and leptin are important modulators of whole-body energy homeostasis that act in the hypothalamus. In a recent paper in Cell Metabolism, González-García et al. demonstrate that CITED1 acts as a key hypothalamic cofactor that mediates the antiobesity effects of estradiol through potentiation of the anorectic actions of leptin.

Astrocytes actively support long-range molecular clock synchronization of segregated neuronal populations.

In mammals, the suprachiasmatic nucleus of the hypothalamus is the master circadian pacemaker that synchronizes the clocks in the central nervous system and periphery, thus orchestrating rhythms throughout the body. However, little is known about how so many cellular clocks within and across brain circuits can be effectively synchronized. In this work, we investigated the implication of two possible pathways: (i) astrocytes-mediated synchronization and (ii) neuronal paracrine factors-mediated synchronization.

Glial Bmal1 role in mammalian retina daily changes.

Visual information processing in the retina requires the rhythmic expression of clock genes. The intrinsic retinal circadian clock is independent of the master clock located in the hypothalamic suprachiasmatic nucleus and emerges from retinal cells, including glia. Less clear is how glial oscillators influence the daily regulation of visual information processing in the mouse retina.

Astrocyte Clocks and Glucose Homeostasis.

The endogenous timekeeping system evolved to anticipate the time of the day through the 24 hours cycle of the Earth's rotation. In mammals, the circadian clock governs rhythmic physiological and behavioral processes, including the daily oscillation in glucose metabolism, food intake, energy expenditure, and whole-body insulin sensitivity. The results from a series of studies have demonstrated that environmental or genetic alterations of the circadian cycle in humans and rodents are strongly associated with metabolic diseases such as obesity and type 2 diabetes.

LC-MS/MS analysis of twelve neurotransmitters and amino acids in mouse cerebrospinal fluid.

Background: So far, analytical investigation of neuroactive molecules in cerebrospinal fluid (CSF) of rodent models has been limited to rats, given the intrinsic anatomic difficulties related to mice sampling and the corresponding tiny amounts of CSF obtained. This poses a challenge for the research in neuroscience, where many, if not most, animal models for neuronal disorders rely on mice.

New Method: We introduce a new, sensitive and robust LC-MS/MS method to analyze a panel of twelve neuroactive molecules (NM) from mouse CSF (aspartic acid, serine, glycine, glutamate, γ-aminobutyric acid, norepinephrine, epinephrine, acetylcholine, dopamine, serotonin, histamine and its metabolite 1-metylhistamine).

Deletion of astrocytic BMAL1 results in metabolic imbalance and shorter lifespan in mice.

Disruption of the circadian cycle is strongly associated with metabolic imbalance and reduced longevity in humans. Also, rodent models of circadian arrhythmia, such as the constitutive knockout of the clock gene Bmal1, leads to metabolic disturbances and early death. Although astrocyte clock regulates molecular and behavioral circadian rhythms, its involvement in the regulation of energy balance and lifespan is unknown.

Astrocytes and Circadian Rhythms: An Emerging Astrocyte-Neuron Synergy in the Timekeeping System.

Animals have an internal timekeeping system to anticipate daily changes associated with the transition of day to night, which is deeply involved in the regulation and maintenance of behavioral and physiological processes. Prevailing knowledge associated the control of circadian clocks to a network of neurons in the central pacemaker, the suprachiasmatic nucleus (SCN), but astrocytes are rapidly emerging as key cellular contributors to the timekeeping system. However, how these glial cells impact the neuronal clock to modulate rhythmic neurobehavioral outputs just begin to be investigated.

Astrocyte deletion of Bmal1 alters daily locomotor activity and cognitive functions via GABA signalling.

Circadian rhythms are controlled by a network of clock neurons in the central pacemaker, the suprachiasmatic nucleus (SCN). Core clock genes, such as Bmal1, are expressed in SCN neurons and in other brain cells, such as astrocytes. However, the role of astrocytic clock genes in controlling rhythmic behaviour is unknown.

Convergent microRNA actions coordinate neocortical development.

Neocortical development is a complex process that, at the cellular level, involves tight control of self-renewal, cell fate commitment, survival, differentiation and delamination/migration. These processes require, at the molecular level, the precise regulation of intrinsic signaling pathways and extrinsic factors with coordinated action in a spatially and temporally specific manner. Transcriptional regulation plays an important role during corticogenesis; however, microRNAs (miRNAs) are emerging as important post-transcriptional regulators of various aspects of central nervous system development.

Fine-Tuning Oligodendrocyte Development by microRNAs.

Myelination of axons by oligodendrocytes in the central nervous system is essential for normal neuronal functions. The failure of remyelination due to injury or pathological insults results in devastating demyelinating diseases. Oligodendrocytes originate in restricted regions of the embryonic ventral neural tube.

Mice deficient in dual oxidase maturation factors are severely hypothyroid.

Dual oxidases (DUOX1 and DUOX2) are evolutionary conserved reduced nicotinamide adenine dinucleotide phosphate oxidases responsible for regulated hydrogen peroxide (H(2)O(2)) release of epithelial cells. Specific maturation factors (DUOXA1 and DUOXA2) are required for targeting of functional DUOX enzymes to the cell surface. Mutations in the single-copy Duox and Duoxa genes of invertebrates cause developmental defects with reduced survival, whereas knockdown in later life impairs intestinal epithelial immune homeostasis.

Role of type 2 deiodinase in response to acute lung injury (ALI) in mice.

Thyroid hormone (TH) metabolism, mediated by deiodinase types 1, 2, and 3 (D1, D2, and D3) is profoundly affected by acute illness. We examined the role of TH metabolism during ventilator-induced lung injury (VILI) in mice. Mice exposed to VILI recapitulated the serum TH findings of acute illness, namely a decrease in 3,5,3'-triiodothyronine (T(3)) and thyroid-stimulating hormone and an increase in reverse T(3).

Thyroid hormone receptor α and regulation of type 3 deiodinase.

Mice deficient in thyroid hormone receptor α (TRα) display hypersensitivity to thyroid hormone (TH), with normal serum TSH but diminished serum T(4). Our aim was to determine whether altered TH metabolism played a role in this hypersensitivity. TRα knockout (KO) mice have lower levels of rT(3), and lower rT(3)/T(4) ratios compared with wild-type (WT) mice.