Joseph Nuñez

Joseph Nuñez
Michigan State University | MSU · Department of Neuroscience

PhD

About

37
Publications
6,631
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2,024
Citations
Citations since 2017
0 Research Items
609 Citations
2017201820192020202120222023020406080100
2017201820192020202120222023020406080100
2017201820192020202120222023020406080100
2017201820192020202120222023020406080100

Publications

Publications (37)
Article
Full-text available
Brain injury during development can have severe, long-term consequences. Using an array of animal models, we have an understanding of the etiology of perinatal brain injury. However, we have only recently begun to address the consequences of endogenous factors such as genetic sex and developmental steroid hormone milieu. Our limited understanding h...
Article
Full-text available
Atrazine (ATR), a commonly used herbicide in the United States, is widely distributed in water and soil because of its mobility through ecosystems and its persistence in the environment. ATR has been associated with defects in sexual development in animals, but studies on mammalian systems have failed to clearly identify a cellular target. Our goal...
Article
The general features of neuroplasticity are developmentally regulated. Although it has been hypothesized that the loss of plasticity in mature neurons may be due to synaptic saturation and functional reduction of N-methyl-D-aspartate receptors (NMDAR), the molecular mechanisms remain largely unknown. We examined the effects of NMDAR activation and...
Article
In this report, we demonstrate that chronic prenatal exposure to a moderate dose of caffeine disrupts novel object recognition and radial arm maze behaviors in adult male and female rats. Pregnant dams were administered either tap water or 75 mg/L caffeinated tap water throughout gestation. Oral self-administration in the drinking water led to an a...
Article
The maturation of the hippocampus is impacted by a multitude of factors, including the regulation of intracellular calcium levels. Depolarizing actions of Gamma-Aminobutyric Acid (GABA) can profoundly alter intracellular calcium in immature hippocampal neurons via influx through voltage-gated calcium channels. We here report fundamental sex differe...
Article
Full-text available
High levels of maternal estrogens are likely to gain access to the fetal brain, yet little is known regarding the role of the steroid hormone 17beta-estradiol in neuronal differentiation and maturation of primate neurons. Previous research documented the presence of estrogen receptors during development in the hippocampus and cortex of the primate...
Article
Brain-derived neurotrophic factor (BDNF) mediates survival and neuroplasticity through the activation of phosphoinositide 3-kinase-Akt pathway. Although previous studies suggested the roles of mitogen-activated protein kinase, phospholipase C-gamma-mediated intracellular calcium ([Ca2+]i) increase, and extracellular calcium influx in regulating Akt...
Article
Numerous studies have documented the consequences of exposure to anesthesia in models of term and post-term infants, evaluating the incidence of cell loss, physiological alterations and cognitive dysfunction. However, surprisingly few studies have investigated the effect of anesthetic exposure on outcomes in newborn rodents, the developmental equiv...
Article
Clinical evidence and animal models indicate greater brain damage in newborn males following injury. In adults, glutamate is the primary source of excitotoxic cell death and the steroid, estradiol, is neuroprotective. In neonatal brain, membrane depolarization following activation of GABAA receptors is the major source of excitation. Consequent inf...
Article
One of the most critical times in the human lifespan is the late embryonic/early postnatal period, due to the careful orchestration of numerous events leading to normal brain development. This period is also characterized by a heightened incidence of harmful events that act via the GABAergic system, including hypoxia-ischemia, seizures and drug exp...
Article
Full-text available
The Morris water maze is widely used to study spatial memory and learning. Animals are placed in a pool of water that is colored opaque with powdered non-fat milk or non-toxic tempera paint, where they must swim to a hidden escape platform. Because they are in opaque water, the animals cannot see the platform, and cannot rely on scent to find the e...
Article
Full-text available
The physiological properties of hippocampal neurons are commonly investigated, especially because of the involvement of the hippocampus in learning and memory. Primary hippocampal cell culturing allows neuroscientists to examine the activity and properties of neurons at the individual cell and single synapse level. In this video, we will demonstrat...
Article
Hypoxia-ischemia is relatively common in human infants. Hypoxia-ischemia can occur as a result of complications associated with prematurity or birth, frequently leading to altered brain development and cognitive and behavioral deficits that persist throughout life. Despite the relative frequency of neonatal hypoxic-ischemic encephalopathy, the imma...
Article
Gamma-aminobutyric acid (GABA) is as an excitatory neurotransmitter during brain development. Activation of GABA(A) receptors in neonatal rat hippocampus results in chloride efflux and membrane depolarization sufficient to open voltage sensitive calcium channels. As development progresses, there is a decline in the magnitude of calcium influx subse...
Article
Hypoxic/ischemic (HI) brain injury in newborn full-term and premature infants is a common and pervasive source of life time disabilities in cognitive and locomotor function. In the adult, HI induces glutamate release and excitotoxic cell death dependent on NMDA receptor activation. In animal models of the premature human infant, glutamate is also r...
Article
Perinatal brain injury is associated with the release of amino acids, principally glutamate and GABA, resulting in massive increases in intracellular calcium and eventual cell death. We have previously demonstrated that independent administration of kainic acid (KA), an AMPA/kainate receptor agonist, or muscimol, a GABA(A) receptor agonist, to newb...
Article
GABA(A) receptor activation during brain development is a critical source of excitation. This is due to the positive equilibrium potential for chloride relative to resting membrane potential, resulting in membrane depolarization sufficient to open voltage sensitive calcium channels. The gonadal steroid estradiol has pronounced trophic effects on th...
Article
Extracellular glutamate levels increase as a consequence of perinatal hypoxia/ischemia, causing the death of neurons and oligodendrocytes. Precursors in the subventricular zone (SVZ) also die following perinatal hypoxia/ischemia; therefore we hypothesized that glutamate would stimulate the death of neural precursors. Here we demonstrate using calci...
Article
Survival rates have increased dramatically for very premature (gestational week 24-28) infants. However, many of these infants grow up to have profound cognitive, motor and behavioral impairments due to brain damage. We have developed a novel model of prenatal infant gray matter injury. During the neonatal period, GABA is an excitatory neurotransmi...
Article
Premature infants are at an exceptionally high risk for brain injury, with damage resulting in permanent behavioral deficits. A contributing factor to the severity of brain injury is gender, with males more sensitive to insult than females. The role of gender and early hormonal environment in addressed in our novel model of prenatal brain damage.
Chapter
This chapter stretches the boundaries in a discussion of neurosteroids and the GABAA receptor: first in that the focus is on estradiol, which, despite being synthesized in the brain, is not considered a classic neurosteroid; and second, in that the primary target of regulation is not the GABAA receptor per se, but rather the consequences of recepto...
Article
Gonadal steroid hormones are known to influence the development of the cerebral cortex of mammals. Steroid hormone action involves hormone binding to cytoplasmic or nuclear receptors, followed by DNA binding and gene transcription. The goals of the present study were twofold: to determine whether androgen receptors are present during development in...
Article
Premature infants are at exceptionally high risk for hypoxic-ischemic insults and other traumatic events that result in permanent brain damage. However, no current models adequately mimic these events. An emerging concept is that the major excitatory drive in immature neurons is derived from depolarizing responses following activation of the gamma-...
Article
Premature infants are at especially high risk for asphyxia, seizures, and other conditions that cause hypoxia-ischemia. These events result in abnormal brain pathology and behavioral deficits that persist throughout adolescence and into adulthood. Current rodent models of human infant hypoxic-ischemic brain damage have focused on exogenous glutamat...
Article
Full-text available
We have developed a model for prenatal hypoxia-ischemia in which muscimol, a selective gamma-aminobutyric acid A (GABA(A)) receptor agonist, administered to newborn rats, induces hippocampal damage. In the neonatal rat brain, activation of GABA(A) receptors leads to membrane depolarization and neuronal excitation. Because of our previous detection...
Article
Premature infants are at exceptionally high risk for hypoxic–ischemic insults and other traumatic events that result in permanent brain damage. However, no current models adequately mimic these events. An emerging concept is that the major excitatory drive in immature neurons is derived from depolarizing responses following activation of the γ-amin...
Article
Premature infants are at especially high risk for asphyxia, seizures, and other conditions that cause hypoxia–ischemia. These events result in abnormal brain pathology and behavioral deficits that persist throughout adolescence and into adulthood. Current rodent models of human infant hypoxic–ischemic brain damage have focused on exogenous glutamat...
Article
Premature and full-term human infants are at considerable risk of excitotoxic-mediated brain damage due to hypoxia-ischemia, infection or other trauma. Glutamate receptor activation is a major source of excitoxicity in the adult and developing brain, and the hippocampus is particularly vulnerable to damage. The seven-day-old rat is a widely used mo...
Article
Previous work from our lab has documented a sex difference in neuron number in the binocular region of the adult rat primary visual cortex (Oc1B), with males having 19% more neurons than females. In the present study, the role of developmental steroid hormones in the formation of this difference was explored. Male and female rats underwent neonatal...
Article
Full-text available
Our previous work has demonstrated that astrocytes in the developing arcuate nucleus of the rat hypothalamus are sexually dimorphic as a result of differential exposure to oestradiol. Moreover, our experiments in neonatal rats suggest an absence of oestrogen receptors (ER) in arcuate nucleus astrocytes in vivo. This, along with the conspicuous lack...
Article
Work from our laboratory has shown that adult male rats have 19% more neurons than female rats in the binocular region and 18% more in the monocular region of the primary visual cortex (Reid and Juraska [1992] J Comp Neurol 321:448-455; Nuñez et al., [1999] Soc Neurosci Abstr 25:229). In the current experiment, we investigated whether cell death in...
Article
We have previously shown that males have more neurons than females in the primary visual cortex, and neonatal androgens play an important role in this difference. Also, we have found that females experience more cell death during development in this region than in males. Therefore, we hypothesized that the neonatal hormone environment directly infl...
Article
Neonatal cryoanesthesia has recently been documented to affect morphology and behavior after a single exposure [Dev. Brain Res. 111 (1998) 89; Horm. Behav. 37 (2000) 169]. In the current experiment, we investigated the effect of one-time exposure to halothane inhalant anesthesia on neonatal rats of both sexes. Fifteen minutes of exposure on postnat...
Article
There is recent evidence that cryoanesthesia, commonly used during neonatal hormone manipulations (e.g., gonadectomy), has deleterious effects on the morphology of the splenium of the corpus callosum and primary visual cortex in adult rats of both sexes. (Nuñez and Juraska, 1998; Nuñez, Kim, and Juraska, 1998). In the present study, the effect of n...
Article
Previous work reported increases in the number of myelinated axons in the splenium of the rat corpus callosum between 25 and 60 days of age. In the present study, we quantified the area occupied by myelinated axons using a light microscopic point counting technique at 60, 120 and 180 days. Myelinated axons increased across these ages (p=0.001). Thu...
Article
The splenium (posterior 1/5) of the corpus callosum is sexually dimorphic in the adult rat brain. In the present study we examined the role of developmental hormones and cryoanesthesia (which is normally used during the performance of neonatal hormone manipulations) on the gross size of the splenium in male and female rats. There was a sex differen...
Article
Hypothermia is often employed as an anesthetic for manipulations of neonatal animals. We previously reported [J. Nuñez, J.M. Juraska, The effect of neonatal cryoanesthesia on the gross size of the splenium of the corpus callosum, Dev. Psychobiol. 30 (1997) 259; J. Nuñez, J.M. Juraska, The size of the splenium of the rat corpus callosum: influence o...

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