Greater Cell Loss Research Articles

Foxn1 and Prkdc genes are important for testis function: evidence from nude and scid adult mice.

Mutations in Foxn1 and Prkdc genes lead to nude and severe combined immunodeficiency (scid) phenotypes, respectively. Besides being immunodeficient, previous reports have shown that nude mice have lower gonadotropins and testosterone levels, while scid mice present increased pachytene spermatocyte (PS) apoptosis. Therefore, these specific features make them important experimental models for understanding Foxn1 and Prkdc roles in reproduction. Hence, we conducted an investigation of the testicular function in nude and scid BALB/c adult male mice and significant differences were observed, especially in Leydig cell (LC) parameters. Although the differences were more pronounced in nude mice, both immunodeficient strains presented a larger number of LC, whereas its cellular volume was smaller in comparison to the wild type. Besides these alterations in LC, we also observed differences in androgen receptor and steroidogenic enzyme expression in nude and scid mice, suggesting the importance of Foxn1 and Prkdc genes in androgen synthesis. Specifically in scid mice, we found a smaller meiotic index, which represents the number of round spermatids per PS, indicating a greater cell loss during meiosis, as previously described in the literature. In addition and for the first time, Foxn1 was identified in the testis, being expressed in LC, whereas DNA-PKc (the protein produced by Prkdc) was observed in LC and Sertoli cells. Taken together, our results show that the changes in LC composition added to the higher expression of steroidogenesis-related genes in nude mice and imply that Foxn1 transcription factor may be associated to androgen production regulation, while Prkdc expression is also important for the meiotic process.

Phrenic Motor Neuron Survival Below a Cervical Spinal Cord Injury

Cervical spinal injury (cSCI) severs descending brainstem projections to spinal respiratory motor neurons, paralyzing respiratory muscles caudal to injury. Spinal hemisection at C2 (C2Hx) has frequently been used as an experimental model of cSCI to study both spontaneous and induced functional recovery of respiratory and non‐respiratory somatic motor function. One assumption implicit in these studies is that C2Hx dennervates motor neurons below the injury, but does not cause significant motor neuron pathology or cell death. However, one recent study reported substantial, bilateral motor neuron death caudal to C2Hx (Satkunendrarajah et al, 2016); in this study, motor neurons were identified by ChAT immunoreactivity in the spinal ventral horn. We have also observed that retrograde labeling with Cholera toxin B fragment (CtB) is diminished in phrenic motor neurons following C2Hx (unpublished data) when the tracer was administered post‐C2Hx. However, these observations are potentially misleading since: 1) C2Hx may diminish ChAT immunoreactivity without motor neuron cell death; and 2) retrograde CtB transport may be diminished following injury due to motor neuron inactivity below the injury, leading to the false impression that phrenic motor neurons had died. Because phrenic motor neuron cell death following cSCI would have profound implications for studies of spontaneous and/or induced phrenic motor plasticity after C2Hx, we tested the hypothesis that C2Hx has minimal impact on phrenic motor neuron cell counts when phrenic motor neurons are retrogradely labeled with CtB prior to cSCI. Phrenic motor neurons were retrogradely labeled in intact adult Sprague Dawley rats via intrapleural injections of CtB. Rats were randomly assigned to one of four groups: 1) 2 week post‐C2Hx, 2) 8 week post‐C2Hx, or 3 & 4) age matched uninjured controls. Two weeks after CtB injection, rats in the C2Hx groups underwent left lateral C2Hx injury under isoflurane anesthesia. Rats were perfused at 2 or 8 wks post‐injury, and longitudinal sections (40 μm) from C3 to C8 were processed to reveal CtB and ChAT. CtB labeled phrenic motor neurons were quantified in serial sections; no loss of phrenic motor neurons was observed at either time post‐C2Hx versus spinally intact rats (p>0.05). Analysis of ChAT immunoreactivity is ongoing; however preliminary data suggest minimal changes in phrenic motor neuron ChAT expression following injury. Although we found little evidence for phrenic motor neuron cell death caudal to C2Hx, we cannot rule out greater cell loss in other motor neuron pools. Consequently, ChAT immunoreactivity is currently underway in non‐phrenic cervical motoneurons caudal to C2Hx. These findings have important implications for studies concerning plasticity in cervical motor systems following cervical spinal injury.Support or Funding InformationSupported by: K12HD055929 (EGR), RO1HL69064 (GSM), T32HD043730 (Allen), and grants from the DoD (GSM), the American Physiological Society (AH, JVS), the McNair Scholars Foundation (JVS), and the McKnight Brain Institute (GSM, MCC).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Phrenic Motor Neuron Survival Caudal to C2 Hemisection

Cervical spinal injury (cSCI) severs descending brainstem projections to spinal respiratory motor neurons, paralyzing respiratory muscles caudal to injury. Spinal hemisection at C2 (C2Hx) has frequently been used as an experimental model of cSCI to study both spontaneous and induced functional recovery of both respiratory and non‐respiratory somatic motor function after cSCI. One assumption implicit in these studies is that C2Hx dennervates motor neurons below the injury, but does not cause significant motor neuron pathology or cell death. However, one recent study reported substantial, bilateral motor neuron death caudal to C2Hx (Satkunendrarajah et al, 2016); in this study, motor neurons were identified by ChAT immunoreactivity in the spinal ventral horn. We have also observed that retrograde labeling with Cholera toxin B fragment (CtB) is diminished in phrenic motor neurons following C2Hx (unpublished data). However, these observations are potentially misleading since: 1) C2Hx may diminish ChAT immunoreactivity without motor neuron cell death; and 2) retrograde transport of CtB may be diminished when administered following an injury, due to the relative inactivity of motor neurons below the injury, giving the false impression that phrenic motor neurons had died. Because phrenic motor neuron cell death following cSCI would have profound implications for studies of spontaneous and/or induced phrenic motor plasticity after C2Hx, we tested the hypothesis that C2Hx has minimal impact on phrenic motor neuron cell counts if phrenic motor neurons are retrogradely labeled with CtB PRIOR to spinal injury. Phrenic motor neurons were retrogradely labeled in intact adult Sprague Dawley rats via intrapleural injections of CtB. Rats were randomly assigned to one of four groups: 1) 2 week C2Hx, 2) 8 week C2Hx, or 3) age matched, spinal intact controls. One week following the CtB injection, rats in the C2Hx groups underwent a left lateral C2Hx injury under isoflurane anesthesia. Rats were then perfused at 2 or 8 weeks post‐injury, and longitudinal sections (40 μm) from C3 to C8 were processed to reveal CtB, ChAT and NeuN. CtB labeled phrenic motor neurons were quantified using a custom MATLAB code. Preliminary analyses suggest minimal loss of phrenic motor neurons at either time post‐C2Hx relative to spinal intact rats. Assessment of ChAT and NeuN immunoreactivity in phrenic motor neurons after C2Hx is ongoing. Although we found little evidence for phrenic motor neuron cell death caudal to C2Hx, we cannot rule out greater cell loss in other motor neuron pools. These findings have important implications for studies concerning motor plasticity following cervical spinal injury.Support or Funding InformationSupported by: T32HD043730, K12HD055929 (EGR), RO1HL69084 (GSM), and grants from the DoD (GSM), and the McKnight Brain Institute (GSM, MCC)

Quantitative and Topographical Analysis of the Losses of Cone Photoreceptors and Retinal Ganglion Cells Under Taurine Depletion.

Taurine depletion is known to induce photoreceptor degeneration and was recently found to also trigger retinal ganglion cell (RGC) loss similar to the retinal toxicity of vigabatrin. Our objective was to study the topographical loss of RGCs and cone photoreceptors, with a distinction between the two cone types (S- and L- cones) in an animal model of induced taurine depletion. We used the taurine transporter (Tau-T) inhibitor, guanidoethane sulfonate (GES), to induce taurine depletion at a concentration of 1% in the drinking water. Spectral-domain optical coherence tomography (SD-OCT) and electroretinograms (ERG) were performed on animals after 2 months of GES treatment administered through the drinking water. Retinas were dissected as wholemounts and immunodetection of Brn3a (RGC), S-opsin (S-cones), and L-opsin (L-cones) was performed. The number of Brn3a+ RGCs, and L- and S-opsin+ cones was automatically quantified and their retinal distribution studied using isodensity maps. The treatment resulted in a significant reduction in plasma taurine levels and a profound dysfunction of visual performance as shown by ERG recordings. Optical coherence tomography analysis revealed that the retina was thinner in the taurine-depleted group. S-opsin+cones were more affected (36%) than L-opsin+cones (27%) with greater cone cell loss in the dorsal area whereas RGC loss (12%) was uniformly distributed. This study confirms that taurine depletion causes RGC and cone loss. Electroretinograms results show that taurine depletion induces retinal dysfunction in photoreceptors and in the inner retina. It establishes a gradient of cell loss depending on the cell type from S-opsin+cones, L-opsin+cones, to RGCs. The greater cell loss in the dorsal retina and of the S-cone population may underline different cellular mechanisms of cellular degeneration and suggests that S-cones may be more sensitive to light-induced retinal toxicity enhanced by the taurine depletion.

Abstract # 1760 Secondary neurodegeneration after stroke is exacerbated by stress: A new opportunity for preserving viable brain tissue

As our population ages stroke is becoming an ever more prevalent condition, afflicting tens of thousands of people every year. The initial stroke event results in a very significant loss of brain tissue at the site of infarction. Unfortunately, however, viable brain tissue continues to be lost after the primary infarction process is complete, in a process known as secondary neurodegeneration (SND). SND involves the progressive death of brain regions that were connected to the original infarcted territories. To better understand SND we have developed a highly controllable model of SND. Specifically, we induce a small stroke within the somatosensory cortex with the assistance of a custom built intrinsic optical signal imaging tandem lens macroscope. This procedure initiates a tightly constrained SND process. We have identified that SND-linked neuroinflammatory disturbances spread out from the injury site, as indicated by significantly enhanced pro-inflammatory signalling (mRNA and protein levels), microglial morphology, neuronal loss (histology), and infiltration of peripheral immune cells (flow cytometry). We have identified that these events are significantly suppressed by chronic stress, or by corticosterone alone, which is in-turn associated with greater cell loss at sites of SND. Collectively, these results suggest that detailed monitoring of stress loads and stress reduction strategies may be warranted in patients recovering from stroke.

The tonotopicity of styrene-induced hearing loss depends on the associated noise spectrum

The neuropharmacological and cochleotoxic effects of styrene can exacerbate the impact of noise on the peripheral auditory receptor. The mechanisms through which co-exposure to noise and styrene impairs hearing are complex as the slowly developing cochleotoxic process can be masked in the short-term by the rapid pharmacological effect on the central nervous system. The current investigation was therefore designed to delineate the auditory frequency range sensitive to noise, to styrene, and to noise and styrene combined. In case of different frequency ranges targeted by noise and styrene, it would be possible to point out the main factor responsible for cases of deafness by looking at the location of the audiometric deficits. Male Brown-Norway rats were exposed to 600-ppm styrene, to an octave band noise centered at 8kHz, or to both noise and styrene. The noise exposure was of two different types: impulse noise with a LEX,8h (equivalent continuous noise level averaged over 8h) of 80dB and continuous noise with a LEX,8h of 85dB SPL. Hearing was tested using a non-invasive technique based on distortion product otoacoustic emissions. Hearing data were completed with histological analysis of cochleae. The results showed that exposure to styrene alone caused outer hair cell losses in the apical cochlear region, which discriminates low frequencies. In contrast, noise-induced hearing loss was located at half an octave above the central frequency of the spectrum, around 10–12kHz. Damage due to impulse noise was significantly exacerbated by styrene, and the noise spectrum defined the location of the cochlear trauma. Combined exposure caused greater cell losses than the sum of losses measured with the impulse noise and styrene alone. The fact that the tonotopicity of the styrene-induced damage depends on the associated noise spectrum complicates the diagnosis of styrene-related hearing loss with a tone-frequency audiometric approach. In conclusion, there is not really a frequency specificity of impairments due to styrene.

Ethanol Promotes Thiamine Deficiency‐Induced Neuronal Death: Involvement of Double‐Stranded RNA‐activated Protein Kinase

Heavy alcohol consumption causes cerebellar degeneration, and the underlying mechanism is unclear. Chronic alcoholism is usually associated with thiamine deficiency (TD) which is known to induce selective neurodegeneration in the brain. However, the role of TD in alcohol-induced cerebellar degeneration remains to be elucidated. The double-stranded RNA-activated protein kinase (PKR) is a potent antiviral protein. Viral infection or binding to dsRNA causes PKR autophosphorylation and subsequent phosphorylation of the alpha-subunit of eukaryotic translation factor-2alpha, leading to inhibition of translation or apoptosis. PKR can also be activated by cellular stresses. In this study, we used an in vitro model, cultured cerebellar granule neurons (CGNs), to investigate the interaction between TD and ethanol and evaluate the contribution of their interaction to neuronal loss. TD was induced by treatment with amprolium in association with ethanol. Cell viability was determined by 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide assay. PKR expression/phosphorylation and subcellular distribution was analyzed with immunoblotting and immunocytochemistry. Thiamine deficiency caused death of CGNs but ethanol did not. However, TD plus ethanol induced a much greater cell loss than TD alone. TD-induced PKR phosphorylation and ethanol exposure significantly promoted TD-induced PKR phosphorylation as well as its nuclear translocation. A selective PKR inhibitor not only protected CGNs against TD toxicity, but also abolished ethanol potentiation of TD-induced loss of CGNs. Ethanol promoted TD-induced PKR activation and neuronal death. PKR may be a convergent protein that mediates the interaction between TD and ethanol.

Altered CNS response to injury in the MRL/MpJ mouse

The MRL/MpJ mouse has a greatly enhanced healing response and an absence of scarring compared with other mouse strains. Following lesions to the CNS mammals show a scarring response known as reactive gliosis, and this CNS scar tissue blocks regeneration of cut axons. We have therefore compared reactive gliosis in the MRL/MpJ mouse and the Swiss Webster mouse, which exhibits normal scarring in the periphery. The lesion model was a stab lesion to the cortex, in which reactive gliosis has previously been quantified. Axon regeneration was examined following a cut lesion to the dopaminergic projection from the substantia nigra to the striatum used in previous regeneration experiments. In the MRL/MpJ following the lesion compared with Swiss Webster mice there was greater cell loss around the lesion followed by greater and more widespread and more prolonged cellular proliferation. Early after the lesion there was a greater loss of glial fibrillary acidic protein (GFAP)-positive astrocytes around the injury site in the MRL/MpJ, and an enhancement and prolongation of the microglial inflammatory response. This was accompanied by greater and more widespread blood–brain barrier leakage following injury. RNA levels for the matrix metalloproteinases (MMP)-2 and MMP-9 as well as for the thrombin receptors PAR-1 and PAR-4 were also greater at the MRL/MpJ injury site. All of these differences were transient and by 14 days post-injury there were no differences observed between MRL/MpJ and control mice. No axonal regeneration was observed following axotomy to the nigrostriatal pathway of the MRL/MpJ or the Swiss Webster mice at any time point.

Comparison of Three Methods for Human Corneal Cryopreservation That Utilize Dimethyl Sulfoxide

We compared endothelial cell survival in human corneas after cryopreservation by three methods that utilize dimethyl sulfoxide. Twenty-eight human cadaver corneas were cryopreserved by one of three methods, stored briefly over liquid nitrogen, thawed, cultured at 37°C for 3 days, and fixed for scanning electron microscopy. Seventeen control corneas underwent identical cryoprotectant immersion and culture protocols but were not frozen. Endothelial photographs taken after 1 and 3 days of culture were analyzed. Endothelial cell losses in cryopreserved corneas by Methods 1, 2, and 3, respectively, were 36, 22, and 10% after 1 day of culture and 57, 36, and 27% after 3 days of culture. Cryopreservation by Method 3 had less cell loss than Methods 1 or 2 (P < 0.02) but greater cell loss than the control corneas for Method 3 (P < 0.001). No loss of cells occurred in the control corneas for Methods 1 and 3 but substantial cell loss (26%) occurred in the control corneas for Method 2. Polymegethism and pleomorphism of the endothelial cells were seen in the corneas that lost cells. The endothelial cell loss of 10% seen after 1 day of culture in human corneas cryopreserved by Method 3 is similar to the loss that occurs during organ culture storage as currently used clinically and therefore would be acceptable for clinical use. After 3 days of culture, however, the cell loss had increased significantly to 27%. This additional decrease in cell number that occurs in culture may represent latent cryodamage and must be understood and overcome in vivo before the technique can be used clinically.

Endothelial Cell Loss Secondary to Two Different Phacoemulsification Techniques

The endothelial cell count after phacoemulsification serves as a sensitive indicator for the level of corneal damage caused by different phacoemulsification techniques. In a prospective and randomized study, the "Reversed Tip and Snip" technique and the "Divide and Conquer" technique were performed in groups of 30 patients each. The corneal endothelial cell count was measured preoperatively as well as 4 weeks and 3 months postoperatively. The endothelial cell count showed significant (P < .001) reduction by approximately 10% after the "Reversed Tip and Snip" technique and by approximately 15% (P < .001) after the "Divide and Conquer" technique. The latter produced a significantly (P < .001) greater cell loss. The "Reversed Tip and Snip" phacoemulsification technique produces less endothelial cell loss than the "Divide and Conquer" technique.

The nucleus basalis (Ch4) in the alcoholic Wernicke-Korsakoff syndrome: reduced cell number in both amnesic and non-amnesic patients

BACKGROUNDThe cholinergic nucleus basalis (Ch4) is an exclusive site of neurofibrillary degeneration in alcoholic patients with Wernicke’s encephalopathy. Aim—To test the hypothesis that the loss of Ch4 neurons contributes to...

Midbrain neuropathology in idiopathic Parkinson's disease and diffuse Lewy body disease

We have quantified midbrain cell loss in idiopathic Parkinson's disease (PD) compared with controls; six patients had PD with onset before 70 years, five patients had late onset PD (>70 years) and nine patients had diffuse Lewy body disease. The pattern of cell loss in these last two groups has not been previously described. No age associated neuronal loss was seen in controls. There was cell loss and reduced area of the pars compacta in all cases but no difference in the pattern of cell loss, which was predominantly ventral. The amount of cell loss in the dorsolateral cluster correlated with the duration of Parkinsonian symptoms, while greater cell loss in the dorsomedial cluster correlated with the presence of tremor and the absence of early dementia. These results suggest that the topography of midbrain pathology does not assist in differentiating these overlapping syndromes.

Organ Culture of a Glioblastoma from a Patient with an Unusually Long Survival

Multicellular tumor spheroids were directly initiated in vitro from the biopsy specimens of a patient who is alive and who has had no neurological changes in 7 years after the gross removal of a glioblastoma. The spheroids were studied alone and in confrontation with aggregates of fetal rat brain tissue. Both in the biopsy and in the tumor spheroids, a very high proportion of cells were proliferating, as flow cytometric deoxyribonucleic acid measurements showed that 40% of the cells in the biopsy specimens and in the tumor spheroids were in the S and G2M phases of the cell cycle. Despite this high proliferation rate, the volume of the spheroids decreased, indicating an even greater cell loss. Light and scanning electron microscopic studies also indicated cell death in the spheroids. This behavior may be related to the long-time survival.

Susceptibility of human foetal brain tissue to cool- and freeze-storage

Human second trimester foetal brain tissue was stored for a period of 1–6 weeks under various conditions in an attempt to evaluate factors influencing its susceptibility (cell loss) and survivability. Post-storage viability of mesencephalon, striatum, cerebellum and occipital cortex was assessed by a protocol combining vital staining with cell density counts so that tissue viability and cell loss could be evaluated simultaneously; tissue survivability was evaluated by cell culture. A significant amount of cell loss occurred after 24 h storage at room temperature, after one week at 4°C and by two weeks at −20°C in all structures; storage at −196°C resulted in 17–21% cell loss at the end of a 6 week period. At −20°C the cryoprotective effect of 20% FCS was equivalent to that of 15% FCS + 7% DMSO combined, suggesting potential use of serum in replacement of chemical additives. The procedure for removal of DMSO was critical to cell viability and survivability: single step dilution led to 27–39% greater cell loss than slow, multi-step dilutions. In comparison to fresh, non-stored tissue, immunocytochemical characterization of in vitro propagated stored tissue revealed no changes in the populations of major constituent cell types including neurones, dopaminergic neurones, glial and fibroblast cells. These results provide information on possible conditions under which transplant tissue can be satisfactorily stored depending on the prevailing requirements.

Effect of 4-bromo-calcium ionophore A23187 on release of Anaplasma marginale from bovine erythrocytes in vitro

SUMMARY The ionophore A23187 was used to facilitate release and continued development of Anaplasma marginale in short-term erythrocyte cultures. Addition of 10 μM A23187 to the cultures resulted in significant decrease in percentage of parasitized erythrocytes (ppe) by 24 hours after treatment; further development and increase in PPE was not observed. In contrast, the ppe of untreated cultures, those treated with dimethyl sulfoxide (dmso) only and with 1 μM A23187 increased slightly during that time. Total erythrocyte count decreased in treated cultures in excess of that expected after samples of the medium were taken for analysis. The greatest cell loss and increased hemoglobin concentration in culture medium was observed in cultures treated with 10 μM A23187 and with an equivalent volume of dmso. The dmso appeared to cause hemolysis of some erythrocytes, but not of infected cells selectively. Release of A marginale inclusion bodies was seen by electron microscopy in samples from the 10 μM A23187-exposed cultures. At 30 minutes after treatment, free initial bodies were frequently seen. Inclusion body membranes and individual A marginale were associated with membranes of adjacent erythrocytes. Individual rickettsiae were seen in cell depressions and appeared to be entering erythrocytes. However, neither further invasion nor development of the parasite in erythrocytes was observed. Ionophore A23187 appeared to promote release of A marginale from erythrocytes, but did not enhance infection of erythrocytes or development of organisms in vitro.

Disease-specific patterns of locus coeruleus cell loss.

Computer visualization techniques were used to map and to quantitatively reconstruct the entire locus coeruleus, including the nucleus subcoeruleus, to compare the topographic patterns of cell loss in postmortem brains from patients with Parkinson's disease, Alzheimer's disease, and Down syndrome. There was comparable cell loss in all three diseases (approximately 60%) compared with aged normal subjects, and there was a significant loss of nucleus subcoeruleus cells specifically in patients with Parkinson's disease (63%). There was a significant positive correlation between the magnitude of locus coeruleus cell loss and the duration of Alzheimer's disease, but no such correlation was found for Parkinson's disease. In patients with Parkinson's disease, there was comparable cell loss throughout the rostral-caudal extent of the nucleus; however, in patients with Alzheimer's disease and Down syndrome, the greatest cell loss always occurred within the rostral portion of the nucleus, with a relative sparing of caudal cells. These data are consistent with the hypothesis that cell loss in Parkinson's disease is the result of a pathological process that attacks the catecholaminergic cells of the locus coeruleus and the subcoeruleus in general; in Alzheimer's disease and Down syndrome, however, the pathological process only affects the rostral, cortical-projecting locus coeruleus cells and spares the caudal, noncortical-projecting cells.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinsonian syndrome in Macaca fascicularis: Which midbrain dopaminergic neurons are lost?

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces, in both human and non-human primates, a syndrome very similar to idiopathic Parkinson's disease. The syndrome is associated with degeneration of the dopamine-containing neurons in the substantia nigra, many of which project to the neostriatum. The purpose of the present study was to quantify the regional distribution of midbrain dopamine neurons remaining after MPTP administration to the monkey ( Macaca fascicularis) and to develop alternative procedures for maintaining the normal nutrition in MPTP-treated animals. Three monkeys were treated with MPTP and three served as controls. Representative sections were examined from rostral to caudal through the midbrain dopamine cell nuclei and the location of every tyrosine hydroxylase-containing cell was entered into a computer. Midbrain dopamine neuronal cell loss ranged from 36–78%, being most extensive in the two monkeys which exhibited the most severe parkinsonian syndrome. The greatest cell loss (46–93%) occurred in the substantia nigra pars compacta, or nucleus A9, and the loss was primarily in the ventral portion of the nucleus. Contrary to most previous reports, however, there was also a loss of cells in the ventral tegmental area (28–57%) and ventral reticular formation (33–87%), corresponding to nuclei A10 and A8, respectively. Since neuroanatomical tracing studies have shown that the dorsal and lateral portions of the striatum (areas showing the greatest dopamine depletion after MPTP) receive input from cells in the ventral A9 and from cells in the A8 and A10 areas, the present data suggest that MPTP preferentially destroys dopamine cells that project to the striatum (i.e. the mesostriatal cells).

Cell degeneration in early development of the forebrain and cerebellum.

The hippocampus, dentate gyrus, cerebellum, amygdala and caudate were examined for degenerating cells in normal neonatal hamsters. Each structure was studied from postnatal day 5 (P5) to P 10. The cerebellum was also studied on P 12. This time span was chosen to coincide with cessation of migration and establishment of connectivity in these structures. Substantial numbers of pycnotic cells were found in all structures except the dentate gyrus. The timing and amount of cell death varied between structures. Both the caudate nucleus and the amygdala showed greater cell losses in their peripheral margins than in their centers. The deep half of the internal granule cell layer of the cerebellum showed greater cell loss than the superficial half on all postnatal days studied.

Simultaneous measurement of cell loss and gastric potential difference in the rat: effects of short-term fasting.

These experiments utilized ex vivo gastric chamber preparations in both fed rats and rats fasted for 14--18 h. A new, simple technique is described for the quantification of cells in small volumes of fluid. The data indicate that exposure to solutions of 50 mM HCl was accompanied by greater cell loss in fasted vs. fed animals. The gastric potential differences of mucosae exposed to Ringer's mammalian saline, and subsequently to 50 mM HCl, were consistently at least 10 mV more negative in fasted animals.