The present MEMRI examination was a safe (i.e., nontoxic) and relatively straightforward procedure that appeared to robustly reflect layer-specific retinal ion demand that correlates with normal retinal physiology responses associated with light and dark visual processing. Comprehensive MEMRI measures of retinal ion demand may be envisioned in a range of animal models for the study of normal development and aging.

Golgi techniques were combined with electron microscopic autoradiography to identify four subpopulations of amacrine cell in the cat retina which accumulate (3H)glycine. These subpopulations include types A3, A4, A7(AII), and A8 amacrine cells. All are narrow-field cells with dendritic spreads of less than 100 micron. Quantification of silver grains showed that each subpopulation exhibits a consistent affinity for (3H)glycine. Type A8 cells were found to have the greatest affinity with normalized grain densities of 0.88-1.0 grains/micron 2 on a scale in which 1.0 represents the most heavily labeled cell. Type A4 cells were moderately labeled with grain densities ranging from 0.40 to 0.68 grains/micron 2. A7(AII) and A3 amacrines were lightly labeled with grain densities of 0.33-0.35 grains/micron 2 and 0.28-0.30 grains/micron 2, respectively.

Brain-derived neurotrophic factor signaling is defective in Angelman syndrome and can be rescued by disruption of Arc/PSD95 binding.

Golgi impregnation techniques were combined with electron microscopic autoradiography of (3H-muscimol in order to provide morphological identification of labeled neurons in the cat retina. This gamma-aminobutyric acid (GABA) agonist has been shown to label the same neurons which accumulate (3H)GABA. Selected cells were photographed and drawn by the aid of a camera lucida drawing tube prior to being thin sectioned for autoradiography. The (3H)muscimol-accumulating neurons which were identified include an interplexiform cell, five classes of conventional amacrine cell, and another cell with its soma located in the ganglion cell layer which is either a ganglion cell or a displaced amacrine. The conventional amacrine cells were compared with the recent morphological classification of Kolb et al. (Vision Res. 21: 1081-1114, '81) and identified as A2, A10, A13, A17, and A19 amacrine cells. These cells exhibit a widespread distribution providing input to all five strata of the inner plexiform layer.

No abstract

The dopamine transporter is the primary means of inactivating synaptic dopamine as well as a major site of action for psychostimulants (such as cocaine and amphetamine) and for neurotoxins that induce parkinsonism. In the present study, a human dopamine transporter partial cDNA clone obtained by polymerase chain reaction exhibited 87% and 89% identity at the nucleic acid and amino acid levels, respectively, with transmembrane domains 3-5 of the rat homolog. This clone was used to quantitate human dopamine transporter mRNA by nuclease protection assay. The postmortem content of dopamine transporter mRNA in the substantia nigrae of 18-to 57-yr-old subjects was relatively constant, while in subjects >57 yr old, a precipitous (>95%) decline in substantia nigra dopamine transporter mRNA was evident. In contrast, tyrosine hydroxylase mRNA in the same samples declined in a linear manner with increasing age. In situ hybridization experiments confirmed the profound loss of dopamine transporter gene expression in melanin-positive (presumptive dopamine) nigral neurons. These data may begin to shed light on compensatory changes occurring in human dopamine neurons during normal aging.The actions of many neurotransmitters are terminated by rapid reuptake into presynaptic nerve endings via neurotransmitter-specific, high-affinity, Na+-dependent membrane transporter proteins. The transporter for the neurotransmitter dopamine (DA) is apparently the receptor through which psychostimulants such as cocaine and amphetamine exert their potent reinforcing properties, leading to psychostimulant abuse and dependence (1). In addition, the DA transporter mediates the active accumulation of neurotoxins such as 1-methyl-4-phenylpyridine into DA neurons (2, 3), resulting in DA cell death and a parkinsonian syndrome. Thus, understanding the regulation of human DA transporter gene expression is an important step toward elucidation of the molecular bases of psychostimulant drug abuse and of neurotoxin-induced (and quite possibly idiopathic) parkinsonism.Ligand binding to the human DA transporter decreases with age (4, 5), in keeping with other evidence for an age-related loss of DA neurons (6). Nevertheless, surprisingly little is known about the nature of normal age-related changes in human DA neurons, a process apparently distinct from the neuronal changes seen in Parkinson disease (6, 7). In the present study, a human DA transporter cDNA clone was obtained by polymerase chain reaction, exploiting predicted sequence homology with the recently cloned, functionally related human norepinephrine transporter (8). With the use of this clone, a precipitous, age-related loss of DA transporter mRNA was observed in human substantia nigra, while tyrosine hydroxylase mRNA, another phenotypic marker of DA neurons, decreased more linearly with age. These data may shed light on some compensatory changes occurring in human DA neurons during the normal aging process. MATERIALS AND METHODSHuman substantia nigrae used for biochemical analyses (n = 36) w...

Autoradiography following 3H-glycine (Gly) uptake and immunocytochemistry with a Gly-specific antiserum were used to identify neurons in Macaca monkey retina that contain a high level of this neurotransmitter. High-affinity uptake of Gly was shown to be sodium dependent whereas release of both endogenous and accumulated Gly was calcium dependent. Neurons labeling for Gly included 40-46% of the amacrine cells and nearly 40% of the bipolars. Synaptic labeling was seen throughout the inner plexiform layer (IPL) but with a preferential distribution in the inner half. Bands of labeled puncta occurred in S2, S4, and S5. Both light and postembedding electron microscopic (EM) immunocytochemistry identified different types of amacrine and bipolar cell bodies and their synaptic terminals. The most heavily labeled Gly+ cell bodies typically were amacrine cells having a single, thick, basal dendrite extending deep into the IPL and, at the EM level, electron-dense cytoplasm and prominent nuclear infoldings. This cell type may be homologous with the Gly2 cell in human retina (Marc and Liu: J. Comp. Neurol. 232:241-260, '85) and the AII/Gly2 of cat retina (Famiglietti and Kolb: Brain Res. 84:293-300, '75; Pourcho and Goebel: J. Comp. Neurol. 233:473-480, '85a). Gly+ amacrines synapse most frequently onto Gly- amacrines and both Gly- and Gly+ bipolars. Gly+ bipolar cells appeared to be cone bipolars because their labeled dendrites could be traced only to cone pedicles. The pattern of these labeled dendritic trees indicated that both diffuse and midget types of biopolars were Gly+. The EM distribution of labeled synapses showed Gly+ amacrine synapses throughout the IPL, but these composed only 11-23% of the amacrine population. Most of the Gly+ bipolar terminals were in the inner IPL, where 70% of all bipolar terminals were labeled. These findings are consistent with previous data from cats and humans and suggest that both amacrine and bipolar cells contribute to glycine-mediated neurotransmission in the monkey retina.

Background: NMDA receptor hyperactivity results in mitochondrial dysfunction in neurons promoting neurodegenerative disorders. Results: Short polyarginine peptides target mitochondria to promote neuronal survival. Conclusion: Short polyarginine peptides reduce mitochondrial respiration, membrane hyperpolarization, and generation of reactive oxygen species. Significance: Treatment with polyarginine has the potential to minimize neuronal damage resulting from stroke or traumatic brain injury and may be therapeutic to ameliorate multiple sclerosis and Parkinson disease.