Biomedical subjects

G M Halliday

Publications and source records attributed to G M Halliday.

At least 163 records · Page 9Linked to original sources

PubMed1992

Brain stem serotonin-synthesizing neurons in Alzheimer's disease: a clinicopathological correlation.

The location and number of brain stem serotonin-synthesizing neurons were analyzed in 11 patients with Alzheimer's disease (AD) and 5 age-matched controls using immunohistochemical techniques. In addition, the number of neuritic plaques and neurofibrillary tangles in the cortex and brain stem raphe was evaluated, as was the number of Nissl-stained raphe neurons. AD patients could be classified into two groups based on their raphe pathology; patients with such pathology (AD+) and those without (AD-). The number of large raphe neurons correlated significantly with the number of serotonin-synthesizing neurons in control material, indicating that all large neurons were serotonergic. This relationship was not apparent in AD+ patients, in whom the number of serotonin-synthesizing neurons correlated with the number of neurofibrillary tangles in the raphe of these patients. This indicates that in AD+ patients the serotonin-synthesizing neurons were selectively affected. There was no correlation between raphe and cortical pathology or raphe pathology and patient sex, age, mini-mental score or depression score, even when such scores were weighted for the interval between testing and death. There was a trend for the raphe pathology to correlate with the age of onset and duration of dementia and the Blessed dementia score in AD+ patients. Most AD+ patients with severe raphe lesions had clinical dementia only, while AD- patients had additional clinical features. The raphe lesions were more dramatic in AD+ patients with a rapid progression of symptoms.

Aged↗

PubMed1992

Topical retinoic acid augments ultraviolet light-induced melanogenesis.

Melanin, the natural pigment found in human skin, absorbs and protects against the ultraviolet (UV) components of sunlight. Melanin production (melanogenesis) is increased by exposure to sunlight, causing a darker skin colour which is regarded as aesthetically pleasing by many humans, who therefore expose themselves to large amounts of potentially damaging sunlight. We have found that topically applied all-trans retinoic acid, a metabolic derivative of vitamin A, greatly enhances UV light-induced melanogenesis: the same preparation on its own had no effect on skin pigmentation. An orally administered retinoid, temarotene, did not have this effect. These observations were made using a lightly pigmented mouse strain, HRA: Skh-2, and confirmed in 2 human volunteers. This is the first time that metabolic derivatives of vitamin A have been shown to augment UV light-induced melanogenesis, suggesting a role for vitamin A in this process.

Animals↗

PubMed1992

Sunscreens protect epidermal Langerhans cells and Thy-1+ cells but not local contact sensitization from the effects of ultraviolet light.

This study compares the ability of two commonly used sunscreens--octyl dimethyl para-aminobenzoate (Padimate O) and 2-ethylhexyl-p-methoxycinnamate (2-EHMC)--to protect Langerhans cells (LC), Thy-1+ dendritic epidermal cells (Thy-1+ dEC), and local contact sensitivity (CS) from the effects of ultraviolet (UV) light. Chronic exposure of mice 5 d per week for 4 weeks with an intermediate dose of solar-simulated sunlight from which any UVC had been filtered reduced the LC and Thy-1+ dEC density of murine epidermis. This irradiation procedure was designed to simulate closely the daily exposure of humans to sunlight. This effect on LC and Thy-1+ dEC occurred in both albino and pigmented mice that develop a tan during the irradiation procedure, indicating that a tan does not protect these cells from the effects of UV light. Sunscreen preparations with Padimate O and 2-EHMC, both of which also contained benzophenone-3, as well as Padimate O or 2-EHMC in organic solvent, inhibited UV light from depleting LC from the epidermis of both mouse strains. Padimate O and 2-EHMC in organic solvent were used to ensure that these were the active ingredients in the sunscreen preparations. In contrast to the effects on LC, Padimate O, but not 2-EHMC, protected Thy-1+ dEC from UV exposure in both mouse strains, but neither protected against the development of local immunosuppression using a contact sensitivity model. Thus, even in a mouse strain that is sensitive to UV-induced immunosuppression, local immunosuppression can occur in the presence of normal densities of LC and Thy-1+ dEC.

Animals↗

PubMed1992

Regulation of the skin immune system by retinoids during carcinogenesis.

One of the immunosuppressive effects of both ultraviolet (UV) light and chemical carcinogens is to deplete Langerhans cells (LC) from the epidermis, suggesting that these cells play an important role in inducing immune responses to developing tumors during the early phases of carcinogenesis. Retinoids such as all-trans-retinoic acid (RA) are natural or synthetic derivatives of vitamin A; RA binds to nuclear receptors in the skin, effecting transcription of a wide range of genes. Topical application of RA prevents the tumor promotor 12-O-tetradecanoylphorbol-13-acetate (TPA) from depleting the density of LC in murine epidermis. In contrast, topical RA did not itself alter the normal LC density. RA also inhibited the development of TPA-induced immunosuppression to a locally applied contact sensitizer. Topical RA also prevented UV light from reducing the density of both LC and Thy-1+ dendritic epidermal cells (Thy-1+ dEC). However, the RA treatment did not prevent local immunosuppression to the contact sensitizer from developing in response to UV irradiation. The reasons for this are unclear, however, it is possible that RA does not inhibit some other immunosuppressive effect of UV light. Temarotene, a recently developed synthetic retinoid also inhibited UV light from reducing the LC and Thy-1+ dEC density from murine epidermis. Thus part of the anti-carcinogenic activity of retinoids may be due to their ability to protect LC during the early stages of carcinogenesis.

Animals↗

PubMed1992

Acceptance of class II major histocompatibility complex disparate skin grafts associated with suppressor cells and elevated Langerhans cell numbers.

Class II major histocompatibility complex (MHC) molecules are only present on Langerhans cells (LC) in normal murine epidermis. Depletion of this antigen with the chemical carcinogen dimethylbenzanthracene (DMBA) causes I-E disparate B10.A(2R) congenic tail skin to be accepted permanently when grafted onto B10.A(4R) recipients. Adoptive transfer of spleen cells from these recipients into naive syngeneic hosts inhibited the ability of the host mice to reject untreated B10.A(2R) tail skin grafts. Hence DMBA-treated LC depleted I-E disparate skin grafts activate suppressor cells which did not inhibit BALB/c mice from rejecting a B10.A(2R) tail skin graft. In contrast, the tobacco derived carcinogen benzo(a)pyrene (BP) increased the number of epidermal LC but had no effect on either class I or class II MHC disparate skin graft survival time. This confirms that the number of class II MHC-positive LC is critical for the initiation of skin graft rejection; when the threshold level is attained graft rejection proceeds at a maximal rate that cannot be enhanced by raising the number of LC. The tolerant skin grafts had increased numbers of LC; this was not observed in syngeneic grafts and therefore may be related to the active suppression of immunity.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1992

Control of Langerhans' cell density by a skin tumour-derived cytokine.

Langerhans' cells (LC) are bone marrow-derived dendritic antigen-presenting cells (APC) found in the epidermis of mammals. It is not known why they accumulate in the epidermis. Human and murine skin tumours are infiltrated with large numbers of LC, however previous experiments have shown that this does not seem to be associated with immune responses against the tumours. Here we show that a squamous-derived tumour cell line (T7) produces a cytokine which increases the number of LC in normal epidermis. T7 supernatant increased the density of LC in both mice syngeneic to the T7 cells (Skh:HR-1) as well as in BALB/c mice, indicating that the cytokine is not genetically restricted. The cytokine is a protein, not a prostaglandin, with a MW of > 12,000 as its production was inhibited by cycloheximide but not indomethacin and it could not be removed by dialysis against a 12,000 MW cut-off membrane. The increased numbers of LC found in tumour supernatant-treated epidermis expressed Ia as well as the molecule defined by the J11d monoclonal antibody, which is expressed by LC but not macrophages, confirming that these cells are LC. Another squamous-derived skin tumour, T79, which is not infiltrated with large numbers of LC when inoculated into syngeneic mice, did not produce a factor capable of increasing the density of LC. Hence these studies demonstrate either the activity of a novel cytokine or a new biological activity of a previously described cytokine. It is most likely that this cytokine increased the number of LC by attracting precursors into the epidermis. As the cytokine was produced by transformed squamous cells it is also possible that this cytokine is responsible for attracting LC into normal epidermis.

Animals↗

PubMed1991

Cytoarchitecture of serotonin-synthesizing neurons in the pontine tegmentum of the human brain.

We have employed immunohistochemical and morphometric procedures to study serotonin-synthesizing (PH8-immunoreactive) neurons in the pontine reticular formation of the adult human. PH8-immunoreactive neurons were found in three cytoarchitectural regions: the median raphe nucleus (MnR), oral pontine reticular nucleus (PnO), and supralemniscal region (group B9). On the basis of cell size, morphology, and position, it was possible to distinguish distinct subgroups within the MnR (dorsal, midline, and paramedian cell clusters) and within the PnO (dorsal and central cell clusters), whereas within the B9 there were no distinct cell clusters. We have estimated that there are approximately 125,000 PH8-immunoreactive neurons in the human pontine tegmentum; 64,400 in the MnR, 30,700 in PnO and 29,000 in B9. The large numbers of serotonin-synthesizing neurons in the human pontine tegmentum contrasts with their relative paucity in nonprimate species such as rats and cats. Nonhuman primates also have large numbers of pontine serotonergic neurons but the morphology of these neurons and their spatial arrangement is significantly different in humans. These results are discussed with respect to the possible projections and functions of these neurons in humans.

Aged↗

PubMed1991

Distribution, morphology and number of monoamine-synthesizing and substance P-containing neurons in the human dorsal raphe nucleus.

The distribution, morphology and number of serotonin-, catecholamine- and substance P-containing neurons in the human dorsal raphe nucleus were studied. Parallel series of sections were prepared from 10 human brainstems obtained at autopsy from patients without neurological disease aged between 42 and 88 years. The neurons were identified using immunohistochemistry with antibodies raised against phenylalanine hydroxylase (tryptophan hydroxylase-containing, serotonin neurons), tyrosine hydroxylase (catecholamine neurons) and substance P. A reference series of Nissl-stained sections was also prepared and data published separately were used to delineate the subnuclear divisions of the dorsal raphe nucleus and to establish the total number of neurons in each subnucleus. The following principal findings emerged. (1) Serotonin-synthesizing neurons are present in all regions of the dorsal raphe nucleus and their total number is 165,000 +/- 34,000. The same types of neurons as those seen in Nissl material characterize each of the five subnuclei (caudal, dorsal, ventral, ventrolateral and interfascicular). (2) Substance P-containing neurons mostly occupy the rostral part of the nucleus and their number is 74,600 +/- 17,600. (3) Catecholamine cells are only found in the rostral part of the dorsal raphe nucleus and their number is 5600 +/- 3400. (4) In the ventral and interfascicular subnuclei the combined number of serotonin-synthesizing and substance P-containing neurons exceeds the total number of Nissl-stained neurons suggesting that serotonin and substance P co-exist in a substantial part of the cell population of the dorsal raphe nucleus. This is further supported by the highly similar morphology and size of these neurons. It is concluded that there are demonstrable chemical differences between the various subregions of the human dorsal raphe nucleus. These differences are in harmony with the results of hodological studies in animals, which have demonstrated differential projection pathways emerging from this nucleus.

Adult↗

PubMed1991

A comparative analysis of neurons containing catecholamine-synthesizing enzymes and neuropeptide Y in the ventrolateral medulla of rats, guinea-pigs and cats.

Neurons in the ventrolateral medulla oblongata of rats, guinea-pigs and cats that contain tyrosine hydroxylase, dopamine-beta-hydroxylase, phenylethanolamine-N-methyltransferase and neuropeptide Y have been demonstrated immunohistochemically in serial coronal sections of tissue taken from the level of the cervical spinal cord to the level of the facial nucleus. The anatomical distribution of these neurons has been described, quantified and reconstructed in three dimensions to compare the neuron populations between species. In all species, between 50 and 90% of immunoreactive neurons lay rostral to the level of the obex. There were no significant differences in the number and distribution of neurons containing catecholamine-synthesizing enzymes between control animals and those pretreated with colchicine, with two exceptions: all dopamine-beta-hydroxylase neurons were weakly immunoreactive without colchicine pretreatment in cats, and pretreatment with colchicine revealed a small rostral group of tyrosine hydroxylase-positive neurons in guinea-pigs. There were remarkable similarities in the rostrocaudal distributions of neurons containing tyrosine hydroxylase, dopamine-beta-hydroxylase and neuropeptide Y in relation to comparable anatomical landmarks across the species. However, the distributions of neurons containing tyrosine hydroxylase. Phenylethanolamine-N-methyltransferase-positive neurons, while densely stained in rats, were only faintly stained in cats and absent in guinea-pigs; the distribution of these neurons was similar to the distribution of neurons containing only tyrosine hydroxylase. The similarity of the distribution of neurons demonstrated using tyrosine hydroxylase, dopamine-beta-hydroxylase and neuropeptide Y immunohistochemistry implies that homologous catecholamine-containing neuron groups do exist in the ventrolateral medulla despite the variation in phenylethanolamine-N-methyltransferase between species. In contrast to the previous classification of neuron groups into A1 and C1 based on the presence or absence of this latter enzyme, the data suggest that a discrete group of tyrosine hydroxylase-immunoreactive neurons, which probably do not contain dopamine-beta-hydroxylase or neuropeptide Y, can be distinguished in the rostral ventrolateral medulla of all species. The absence of detectable dopamine-beta-hydroxylase in this group of neurons suggests that they may not synthesize either adrenaline or noradrenaline.

Animals↗

PubMed1991

Four groups of tyrosine hydroxylase-immunoreactive neurons in the ventrolateral medulla of rats, guinea-pigs and cats identified on the basis of chemistry, topography and morphology.

The data in the preceding paper [Halliday G. M. and McLachlan E. M. (1991) Neuroscience 43, 531-550] suggest that some neurons in the rostral ventrolateral medulla contain some catecholamine-synthesizing enzymes but may not produce catecholamines. The present study addresses this question directly by comparing the anatomical location and morphology of these neurons with those revealed by formaldehyde-induced fluorescence. Catecholamine-containing somata of rats and guinea-pigs have been demonstrated following FAGLU-perfusion in normal untreated animals, in animals pretreated with pargyline (a monoamine oxidase inhibitor), and in animals pretreated with colchicine (to block axoplasmic transport). The number and location of fluorescent somata in the ventrolateral medulla have been determined in serial coronal sections of tissue from the cervical spinal cord to the level of the facial nucleus. Catecholamine-fluorescent neurons at different levels of the ventrolateral medulla varied in their topography and sensitivity to pharmacological manipulation. However, the rostrocaudal distributions in rats and guinea-pigs were quantitatively remarkably similar implying that homologous groups of catecholamine-containing neurons exist. Comparison between these distributions and those of somata stained immunohistochemically for catecholamine-synthesizing enzymes and neuropeptide Y [Halliday G. M. and McLachlan E. M. (1991) Neuroscience 43, 531-550] revealed that the majority of fluorescent neurons in both species probably contain dopamine-beta-hydroxylase and neuropeptide Y as well as tyrosine hydroxylase. Those neurons lying just caudal to the facial nucleus immunoreactive for tyrosine hydroxylase and phenylethanolamine-N-methyltransferase but not dopamine-beta-hydroxylase and neuropeptide Y also lack catecholamine fluorescence. This rostral group of somata can be identified immunohistochemically in cats. The size and morphology of catecholamine-fluorescent neurons have been analysed in detail, and compared with the same features of the immunohistochemically stained neurons. Three morphological types of catecholamine-containing neurons could be distinguished in material prepared by both techniques from rats and guinea-pigs, and in immunohistochemical material from cats. Rostral tyrosine hydroxylase-positive neurons, which differed morphologically from these three types, were present in all three species. On the basis of anatomical location, neuronal morphology and chemical characteristics, four groups of tyrosine hydroxylase-immunoreactive neurons have been identified in the ventrolateral medulla of rats, guinea-pigs and cats. Only the caudal three of these four groups appear to synthesize catecholamine, probably noradrenaline. From published data it seems likely that these four groups of tyrosine hydroxylase-positive neurons have distinct projections and functions related to cardiovascular and respiratory control.

Animals↗

PubMed1991

Substance P-containing neurons in the mesopontine tegmentum are severely affected in Parkinson's disease.

Substance P immunoreactive (SP+) neurons were analysed quantitatively in serial sections of the mesopontine tegmentum in 6 patients with idiopathic Parkinson's disease and 5 age-matched normal controls. In the tegmentum of the Parkinson's disease brains many SP+ neurons contained swollen, twisted neuronal processes as well as Lewy bodies. There were significant reductions in the total number of SP+ neurons in the pedunculopontine tegmental nucleus (loss 43%), in the laterodorsal tegmental nucleus (loss 28%), in the oral pontine reticular nucleus (loss 41%) and in the median raphe nucleus (loss 76%). It was the large SP+ (greater than 20 microns) neurons that were particularly affected. In our control group we did not document a significant relationship between age at death and number of SP+ neurons in these tegmental nuclei or between age at death and number of pigmented neurons in the locus coeruleus. In contrast, in patients with Parkinson's disease, there was a strong inverse relationship between age at death and numbers of SP+ and pigmented neurons. Our findings suggest an interaction between the pathophysiological mechanisms initiated by Parkinson's disease and other processes related to ageing. Since tegmental SP+ neurons are affected by the primary pathological processes underlying Parkinson's disease as severely as catecholamine-synthesizing neurons are affected, theories of pathogenesis and therapeutic strategies in Parkinson's disease will need to take into account the involvement of these SP+ neurons.

Aged↗

PubMed1991

Immunocytochemical analysis of the cellular infiltrate in primary regressing and non-regressing malignant melanoma.

Spontaneous regression occurs in a small proportion of malignant melanomas, and it is important to understand the processes involved in its induction as this may give a guide to future therapies for this disease. We have examined 36 primary malignant melanomas (19 regressing, 17 non-regressing) and identified the cellular phenotypes and activation states of the cells infiltrating regressing and non-regressing primary melanomas by immunochemistry. We have found a significantly increased number of CD3-positive cells and an increased ratio of CD4/CD8-positive cells infiltrating regressing compared to non-regressing tumors. In addition, the expression of the interleukin 2 receptor, an activation marker for T cells, was increased. However, there were no significant differences in class II MHC, CD1, intercellular adhesion molecule 1 (ICAM1), or melanoma-associated differentiation-antigen expression in these tumors. These data are consistent with melanoma regression being induced by activated CD4 T cells and do not seem to be related to the differentiation markers we have examined on these tumors.

Antibodies, Monoclonal↗

PubMed1991

Langerhans cell migration into ultraviolet light-induced squamous skin tumors is unrelated to anti-tumor immunity.

There has been much speculation as to the role of Langerhans cells (LC) in the induction of anti-tumor immunity. Whereas there is considerable circumstantial evidence that disruptions in the density and function of these cells during the early stages of ultraviolet (UV) light- and chemical carcinogen-induced carcinogenesis may be important for enabling developing neoplasms to escape immune destruction, the role of the large number of these cells found infiltrating developed skin tumors is less clear. To investigate this we have compared the LC density infiltrating transplanted non-immunogenic and immunogenic UV-induced murine tumors as well as LC in the epidermis overlying the tumors. Whereas two non-immunogenic tumor lines attracted large numbers of Ia+ dendritic cells, an immunogenic tumor line did not. Similar results were obtained whether the tumors were transplanted into syngeneic immunocompetent or athymic immunodeficient mice. Hence, there was no relationship between tumor immunogenicity or host immunocompetence and Ia+ dendritic cell density. Furthermore, there was no correlation with the pattern of T-cell infiltration of the tumors or CD4/CD8 cell ratio. Our results also indicate that whereas UV light decreased Ia+ cell density, both in the epidermis and the tumors, it did not inhibit the tumors from attracting Ia+ dendritic cells. Thus, the Ia+ dendritic cells infiltrating skin tumors are unlikely to indicate a host immune response to the tumor, but are more likely to be attracted by tumor-derived cytokines.

Animals↗

PubMed1991

Indomethacin inhibits the chemical carcinogen benzo(a)pyrene but not dimethylbenz(a)anthracene from altering Langerhans cell distribution and morphology.

Treatment of murine skin with the polyaromatic hydrocarbon carcinogens benzo(a)pyrene (BP) or dimethylbenz(a)anthracene (DMBA) for 3 weeks resulted in an increase and a decrease in epidermal Langerhans cell (LC) numbers, respectively, compared with solvent-treated skin. Implantation of subcutaneous indomethacin pellets prior to carcinogen treatment prevented the changes in LC numbers and morphology in BP, but not DMBA-treated skin. Indomethacin treatment was also found to reduce elevated prostaglandin E2 (PGE)2 levels in the skin of BP-treated mice, whereas PGE2 levels were not significantly raised in DMBA-treated mice. There thus appears to be a link between altered prostaglandin levels and LC numbers in murine skin treated with BP, but not DMBA. In the latter, LC numbers were reduced by mechanisms not reversed by indomethacin. It is concluded that increased prostaglandin levels may contribute to the impairment of cutaneous immunity previously observed in BP-treated mice by altering LC density and morphology within the epidermis.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1991

A role for prostaglandins in the suppression of cutaneous cellular immunity and tumour development in benzo(a)pyrene- but not dimethylbenz(a)anthracene-treated mice.

Prostaglandins have been implicated in the immune suppression associated with the development of some tumours. Application of the prostaglandin synthetase inhibitor indomethacin, to murine skin prior to treatment with the chemical carcinogens benzo(a)pyrene (BP) or 7,12 dimethylbenz(a)anthracene (DMBA), restored contact sensitivity responses to 2,4-dinitrofluorobenzene in BP- but not DMBA-treated mice. However, indomethacin failed to restore antibody responses in either group of mice. Prolonged treatment with BP or DMBA led to cutaneous tumour formation. Indomethacin was found to delay the onset and reduce the size of tumours in BP- but not DMBA-treated mice. It is proposed that prostaglandin-induced suppression of cellular cutaneous immunity may play a role in BP- but not DMBA-induced cutaneous carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1991

Langerhans cell depletion in gliotoxin-treated murine epidermis.

Langerhans cells (LC) are dendritic antigen presenting cells of bone marrow origin which reside in the suprabasal layer of the epidermis. They express high concentrations of Class II MHC glycoproteins on their plasma membrane and transport cutaneous antigen to local lymph nodes for presentation to helper T cells. They are thus essential for the induction of cutaneous immunity. Gliotoxin is a member of the epipolythiodioxopiperazine (ETP) group of fungal metabolites, derived from the human pathogen Aspergillus fumigatus. It has been shown to have immunomodulating properties in vivo and in vitro, and has been proposed as a potential immunosuppressant for transplantation therapy. Epicutaneous application of gliotoxin reduced the numbers of epidermal LC by 30-35 per cent with an associated morphological change from highly dendritic to a more rounded form. Electron microscopic studies showed selective damage to LC at very low (nM) concentrations of gliotoxin, with no obvious effect on adjacent keratinocytes. LC numbers remained depleted for 13 weeks after initial treatment, suggesting that systemic suppression or prolonged retention of gliotoxin within the skin may play a role in its mechanism of action.

Animals↗

PubMed1991

Topical and oral retinoids protect Langerhans' cells and epidermal Thy-1+ dendritic cells from being depleted by ultraviolet radiation.

Murine epidermis contains two types of bone marrow-derived cells of the immune system, Langerhans' cells (LC), which are dendritic antigen-presenting cells, and Thy-1+ dendritic cells (Thy-1+ DEC), which express the gamma/delta T-cell receptor for antigen and hence are probably T cells whose function in the epidermis is unknown. Ultraviolet (UV) light greatly reduces the density of both of these cell types, and hence this may be one of the mechanisms by which UV light induces immunosuppression. It is important to develop strategies for protecting these cells from the effects of UV light. In this study we show that topical all-trans-retinoic acid (RA) and an orally administered retinoid, temarotene, protect both LC and Thy-1+ DEC from being depleted by UV light. However, neither retinoid inhibited the development of immunosuppression in response to application of a contact sensitizer. We also compared two congenic mouse strains, one albino, the other lightly pigmented and capable of tanning in response to UV light. There was no difference in the ability of UV light to deplete LC or Thy-1+ DEC in these two strains or of retinoids to inhibit their depletion. These studies demonstrate that retinoids but not melanin are able to inhibit UV light from depleting LC and Thy-1+ DEC; however, there are other immunosuppressive effects of UV light which are not protected by the retinoids.

Animals↗

PubMed1990

Cytoarchitecture of the human dorsal raphe nucleus.

Serial 50 microns Nissl-stained sections through the midbrain and pontine central gray of four adult humans (mean age 56 years, mean postmortem delay 3 hours) were analysed and the subnuclei of the dorsal raphe nucleus (DR) delineated on the basis of neuronal morphology and density. Five subnuclei were apparent: the interfascicular, ventral, ventrolateral, dorsal, and caudal. The area of each subnucleus was measured in sections selected at regular intervals throughout the length of the DR. The number of neurons was counted and their density within each subnucleus calculated. The dorsal subnucleus was the largest and contained the majority of neurons but had the lowest neuronal density. The ventrolateral subnucleus had the highest density of neurons. A total of 235,000 +/- 15,000 neurons (average of 1,200 +/- 200 neurons per section) were found within a volume of 71.3 +/- 4.5 mm3 of DR with a mean neuronal density of 3,300 +/- 200 neurons/mm3. Morphometric and morphological analysis of DR neurons revealed four distinct neuron types: round, ovoid, fusiform, and triangular. These types of neurons characterized particular subnuclei. The location and boundaries of the subnuclei of the human dorsal raphe are presented in the form of an atlas. The subdivisions described are similar to that described in other mammals. On the basis of this information the location of particular projection neurons within the human dorsal raphe can be predicted and the effects of disease on this nucleus may be forecast.

Animals↗